Trial Outcomes & Findings for B Cell Response to a Primary and a Booster Course of the Novartis Meningococcal ACWY Conjugate Vaccine in Healthy Infants (NCT NCT00488683)

Last Updated: 2014-10-01

Results Overview

The memory B cell response at one month after primary vaccinations (5 months of age) was defined as the mean number of meningococcal serogroup A, C, W-135 and Y specific memory B cells, measured in vitro by ELISpot assay per 2x100000 lymphocytes obtained from culture (LOC) of peripheral blood mononuclear cells (PBMC) circulating in blood incubated for 5.5 days in the presence of polyclonal B cell activators. Serogroup A, C, W-135 and Y geometric mean titers (GMTs) were measured by serum bactericidal assay using human complement (hSBA) at 12 months of age (before third dose). Correlation and linear regression coefficients were determined between memory B cells at 1 month after primary vaccinations with MenACWY-CRM (5 months of age) and hSBA titers at 12 months of age (before third dose) for the serogroups A, C, W-135 and Y.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

216 participants

Primary outcome timeframe

1 month after primary vaccination and immediately before third dose at 12 months of age

Results posted on

2014-10-01

Participant Flow

Subjects were enrolled at one study center in the UK.

All enrolled subjects were included in the trial.

Participant milestones

Participant milestones
Measure	MenACWY-CRM and Routine Vaccines (Group 1) Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Overall Study STARTED	108	54	54
Overall Study COMPLETED	96	48	52
Overall Study NOT COMPLETED	12	6	2

Reasons for withdrawal

Reasons for withdrawal
Measure	MenACWY-CRM and Routine Vaccines (Group 1) Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Overall Study Withdrawal by Subject	1	2	2
Overall Study Lost to Follow-up	5	3	0
Overall Study Protocol Violation	5	1	0
Overall Study Unable to Classify	1	0	0

Baseline Characteristics

B Cell Response to a Primary and a Booster Course of the Novartis Meningococcal ACWY Conjugate Vaccine in Healthy Infants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MenACWY-CRM and Routine Vaccines (Group 1) n=108 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) n=54 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) n=54 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.	Total n=216 Participants Total of all reporting groups
Age, Continuous	60.5 Days STANDARD_DEVIATION 3.7 • n=5 Participants	59.8 Days STANDARD_DEVIATION 3.6 • n=7 Participants	59.8 Days STANDARD_DEVIATION 3.6 • n=5 Participants	60.2 Days STANDARD_DEVIATION 3.7 • n=4 Participants
Sex: Female, Male Female	48 Participants n=5 Participants	28 Participants n=7 Participants	25 Participants n=5 Participants	101 Participants n=4 Participants
Sex: Female, Male Male	60 Participants n=5 Participants	26 Participants n=7 Participants	29 Participants n=5 Participants	115 Participants n=4 Participants
Race/Ethnicity, Customized Caucasians	95 Subjects n=5 Participants	47 Subjects n=7 Participants	51 Subjects n=5 Participants	193 Subjects n=4 Participants
Race/Ethnicity, Customized Black	2 Subjects n=5 Participants	2 Subjects n=7 Participants	0 Subjects n=5 Participants	4 Subjects n=4 Participants
Race/Ethnicity, Customized Asian	1 Subjects n=5 Participants	1 Subjects n=7 Participants	0 Subjects n=5 Participants	2 Subjects n=4 Participants
Race/Ethnicity, Customized Others	10 Subjects n=5 Participants	4 Subjects n=7 Participants	3 Subjects n=5 Participants	17 Subjects n=4 Participants

PRIMARY outcome

Timeframe: 1 month after primary vaccination and immediately before third dose at 12 months of age

Population: Analysis was performed on per-protocol (PP) dataset of primary vaccination, i.e. subjects who received all the relevant doses of vaccine correctly; provided evaluable blood samples at the relevant time points; and had no major protocol violation as defined prior to analysis.

Outcome measures

Outcome measures
Measure	MenACWY-CRM and Routine Vaccines (Group 1) n=88 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) n=34 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) n=50 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Summary of Memory B Cells Per 2 x 105 LOC by Serogroup A, C, W-135 and Y Serogroup A (N=50,25,30)	2.10 B cells per 2x100000 lymphocytes Standard Deviation 2.03	1.80 B cells per 2x100000 lymphocytes Standard Deviation 1.27	1.72 B cells per 2x100000 lymphocytes Standard Deviation 1.89
Summary of Memory B Cells Per 2 x 105 LOC by Serogroup A, C, W-135 and Y Serogroup C (N=71,31,43)	2.57 B cells per 2x100000 lymphocytes Standard Deviation 2.73	1.71 B cells per 2x100000 lymphocytes Standard Deviation 1.12	2.43 B cells per 2x100000 lymphocytes Standard Deviation 2.32
Summary of Memory B Cells Per 2 x 105 LOC by Serogroup A, C, W-135 and Y Serogroup W-135 (N=62,26,40)	2.39 B cells per 2x100000 lymphocytes Standard Deviation 4.69	1.50 B cells per 2x100000 lymphocytes Standard Deviation 0.721	1.57 B cells per 2x100000 lymphocytes Standard Deviation 1.47
Summary of Memory B Cells Per 2 x 105 LOC by Serogroup A, C, W-135 and Y Serogroup Y (N=54,25,30)	2.91 B cells per 2x100000 lymphocytes Standard Deviation 8.36	1.43 B cells per 2x100000 lymphocytes Standard Deviation 0.71	1.78 B cells per 2x100000 lymphocytes Standard Deviation 1.67

SECONDARY outcome

Timeframe: 1 month after primary vaccination and immediately before third dose

Population: Analysis was performed on PP dataset of persistence population.

Memory B cell response at 1 month after primary vaccination and immediately before third dose at 12 months of age was measured as mean number of meningococcal serogroup specific memory B cells by ELISpot assay per 2x100000 LOC. The meningococcal serogroup A, C, W-135 and Y specific IgG concentrations immediately before third dose at 12 months of age were measured by ELISA.

Outcome measures

Outcome measures
Measure	MenACWY-CRM and Routine Vaccines (Group 1) n=79 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) n=37 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) n=39 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Memory B Cells by Serogroup A, C, W-135 and Y	NA (NUMBER) Outcomes are based on correlation and regression coefficients.	NA (NUMBER) Outcomes are based on correlation and regression coefficients.	NA (NUMBER) Outcomes are based on correlation and regression coefficients.

SECONDARY outcome

Timeframe: 1 month after primary vaccination and 1 month after third vaccination

Population: Values from Group 1 were analyzed separately. Values from Groups 2 and 3 were combined for the analysis. Groups 2 and 3 received PCV at 12 months while Group 1 received PCV at 13 months. Analysis was performed on PP booster population.

Memory B cell response at 1 month after MenACWY-CRM primary and booster vaccinations was measured as mean number of meningococcal serogroup specific memory B cells by ELISpot assay per 2x100000 LOC. hSBA GMTs for the serogroup A, C, W-135 and Y were measured one month after the third MenACWY-CRM vaccination. The meningococcal serogroup A, C, W-135 and Y specific IgG concentrations one month after third MenACWY-CRM vaccination were measured by ELISA.

Outcome measures

Outcome measures
Measure	MenACWY-CRM and Routine Vaccines (Group 1) n=85 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) n=40 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) n=42 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Memory B Cells Per 2x100000 by Serogroup A,C, W-135 and Y at One Month After Primary MenACWY-CRM Vaccination and Third MenACWY-CRM Vaccination	NA (NUMBER) Outcomes are based on correlation and regression coefficients.	NA (NUMBER) Outcomes are based on correlation and regression coefficients.	NA (NUMBER) Outcomes are based on correlation and regression coefficients.

SECONDARY outcome

Timeframe: 1 month after primary and pre-third and 1 month after third vaccination

Memory B cell response at 1 month after MenACWY-CRM primary and third (booster) vaccination was measured as mean number of meningococcal serogroup specific memory B cells by ELISpot assay per 2x100000 LOC. The serogroup A, C, W-135 and Y specific IgG concentrations at 1 month after MenACWY-CRM booster were measured by ELISA. hSBA GMTs were measured by hSBA assay one month after MenACWY-CRM booster vaccination. The rise in serogroup specific IgG, memory B cells and hSBA was calculated by pre/post third dose geometric mean ratios, calculated by the difference in the log10 of the concentrations/titers measured at 13 months to the log10 of the concentrations at 12 months: i.e. rise = log10(x) at 13 months minus log10(x)at 12 months where x is the serogroup specific IgG or memory B cell concentrations or SBA titers.

Outcome measures

Outcome measures
Measure	MenACWY-CRM and Routine Vaccines (Group 1) n=85 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) n=40 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) n=42 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Memory B Cells 1 Month After Primary Vaccination and Rise From Pre-third Dose to 1 Month After Third Dose of MenACWY-CRM Vaccination	NA (NUMBER) Outcomes are based on correlation and regression coefficients.	NA (NUMBER) Outcomes are based on correlation and regression coefficients.	NA (NUMBER) Outcomes are based on correlation and regression coefficients.

SECONDARY outcome

Timeframe: One month after primary vaccination and 1 week after third vaccination

Population: This outcome was assessed in Group 3 subjects only as they provided a blood draw at 1 week following the MenACWY-CRM booster vaccination. Analysis was performed on PP booster population.

Memory B cell response at 1 month after primary vaccination and at 1 week after third vaccination was measured as mean number of meningococcal serogroup specific memory B cells by ELISpot assay per 2x100000 LOC. Plasma B cell response at 1 week after vaccination was measured as the mean number of cells secreting antibodies specific for meningococcal serogroup A, C, W-135 and Y, measured by ELISpot assay, per 2x100000 PBMC. Serogroup A, C, W-135 and Y specific IgG were measured by ELISA and hSBA GMTs were measured at 1 week after third vaccination.

Outcome measures

Outcome measures
Measure	MenACWY-CRM and Routine Vaccines (Group 1) Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) n=42 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Memory B Cells 1 Month After Primary Vaccination and 1 Week After Third Vaccination by Serogroup A, C, W-135 and Y	—	—	NA (NUMBER) Outcomes are based on correlation and regression coefficients.

SECONDARY outcome

Timeframe: 5 months (B cells), 12 months and 13 months (B cells and IgG) of age

Population: Analysis was done on the PP primary population and PP booster population.

CRM197 specific memory B cell response at each time point was measured as mean number of CRM197 specific memory B cells by ELISpot assay per 2x100000 LOC. CRM197 specific IgG concentration was measured by ELISA at 12 months of age and one month after MenACWY-CRM booster vaccination.

Outcome measures

Outcome measures
Measure	MenACWY-CRM and Routine Vaccines (Group 1) n=85 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) n=40 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) n=42 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
CRM197 Specific Memory B Cells 1 Month After Primary Vaccination and at 12 Months of Age and One Month After MenACWY-CRM Third Vaccination	NA (NUMBER) Data were not summarized for each group as correlation and regression deal with relationships among two variables measured on each subject rather than a summary measure (e.g. mean) per vaccine group.	NA (NUMBER) Data were not summarized for each group as correlation and regression deal with relationships among two variables measured on each subject rather than a summary measure (e.g. mean) per vaccine group.	NA (NUMBER) Data were not summarized for each group as correlation and regression deal with relationships among two variables measured on each subject rather than a summary measure (e.g. mean) per vaccine group.

SECONDARY outcome

Timeframe: Before and one month after booster vaccination

Population: Analysis was performed on the PP dataset of booster vaccination.

Memory B cell response before and one month after MenACWY-CRM booster vaccination at 12 months of age was measured as mean number of meningococcal serogroup A, C, W-135 and Y specific memory B cells by ELISpot assay per 2x100000 LOC.

Outcome measures

Outcome measures
Measure	MenACWY-CRM and Routine Vaccines (Group 1) n=85 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) n=40 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) n=42 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Increase in Serogroup A, C, W-135 and Y Specific Memory B Cells Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup A specific B cells (N=58,29,31) before	1.811 B cells per 2x100000 lymphocytes Standard Deviation 1.935	1.988 B cells per 2x100000 lymphocytes Standard Deviation 1.881	1.692 B cells per 2x100000 lymphocytes Standard Deviation 1.398
Increase in Serogroup A, C, W-135 and Y Specific Memory B Cells Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup A specific B cells (N=54,26,33) after	6.429 B cells per 2x100000 lymphocytes Standard Deviation 6.365	6.527 B cells per 2x100000 lymphocytes Standard Deviation 5.957	7.488 B cells per 2x100000 lymphocytes Standard Deviation 12.512
Increase in Serogroup A, C, W-135 and Y Specific Memory B Cells Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup C specific B cells (N=75,35,38) before	2.076 B cells per 2x100000 lymphocytes Standard Deviation 1.926	1.983 B cells per 2x100000 lymphocytes Standard Deviation 1.482	2.188 B cells per 2x100000 lymphocytes Standard Deviation 2.004
Increase in Serogroup A, C, W-135 and Y Specific Memory B Cells Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup C specific B cells (N=73,37,40) after	9.437 B cells per 2x100000 lymphocytes Standard Deviation 10.861	8.907 B cells per 2x100000 lymphocytes Standard Deviation 9.791	8.915 B cells per 2x100000 lymphocytes Standard Deviation 10.830
Increase in Serogroup A, C, W-135 and Y Specific Memory B Cells Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup W specific B cells (N=75,34,38) before	1.783 B cells per 2x100000 lymphocytes Standard Deviation 2.189	1.793 B cells per 2x100000 lymphocytes Standard Deviation 1.531	2.067 B cells per 2x100000 lymphocytes Standard Deviation 2.616
Increase in Serogroup A, C, W-135 and Y Specific Memory B Cells Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup W specific B cells (N=73,37,39) after	6.205 B cells per 2x100000 lymphocytes Standard Deviation 6.776	4.430 B cells per 2x100000 lymphocytes Standard Deviation 5.939	5.201 B cells per 2x100000 lymphocytes Standard Deviation 6.648
Increase in Serogroup A, C, W-135 and Y Specific Memory B Cells Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup Y specific B cells (N=67,33,34) before	2.172 B cells per 2x100000 lymphocytes Standard Deviation 2.934	1.556 B cells per 2x100000 lymphocytes Standard Deviation 0.898	1.749 B cells per 2x100000 lymphocytes Standard Deviation 1.797
Increase in Serogroup A, C, W-135 and Y Specific Memory B Cells Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup Y specific B cells (N=64,32,34) after	6.950 B cells per 2x100000 lymphocytes Standard Deviation 9.122	6.603 B cells per 2x100000 lymphocytes Standard Deviation 8.198	5.746 B cells per 2x100000 lymphocytes Standard Deviation 12.624

SECONDARY outcome

Timeframe: Before and one month after booster vaccination

Population: Analysis was performed on the PP dataset of booster vaccination.

hSBA GMTs were measured before and one month after MenACWY-CRM booster vaccination at 12 months of age.

Outcome measures

Outcome measures
Measure	MenACWY-CRM and Routine Vaccines (Group 1) n=85 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) n=40 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) n=42 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Increase in Serogroup A, C, W-135 and Y Specific hSBA Titers Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup C - hSBA GMT (N=78,39,40)- after	315 titers Interval 239.0 to 417.0	217 titers Interval 138.0 to 341.0	308 titers Interval 214.0 to 445.0
Increase in Serogroup A, C, W-135 and Y Specific hSBA Titers Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup A - hSBA GMT - before	2.2 titers Interval 2.05 to 2.36	2 titers Interval 2.0 to 2.0	2.14 titers Interval 1.93 to 2.37
Increase in Serogroup A, C, W-135 and Y Specific hSBA Titers Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup A - hSBA GMT - after	65 titers Interval 47.0 to 89.0	48 titers Interval 32.0 to 72.0	67 titers Interval 44.0 to 102.0
Increase in Serogroup A, C, W-135 and Y Specific hSBA Titers Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup C - hSBA GMT (N=83,39,40)- before	5.56 titers Interval 4.23 to 7.3	4.83 titers Interval 3.28 to 7.09	5.61 titers Interval 3.78 to 8.33
Increase in Serogroup A, C, W-135 and Y Specific hSBA Titers Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup W - hSBA GMT (N=67,37,34)- before	8.4 titers Interval 6.03 to 12.0	12 titers Interval 8.05 to 17.0	10 titers Interval 6.73 to 15.0
Increase in Serogroup A, C, W-135 and Y Specific hSBA Titers Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup W - hSBA GMT (N=67,37,34)- after	889 titers Interval 622.0 to 1271.0	649 titers Interval 419.0 to 1004.0	602 titers Interval 343.0 to 1057.0
Increase in Serogroup A, C, W-135 and Y Specific hSBA Titers Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup Y - hSBA GMT (N=43,25,16)- before	8.71 titers Interval 5.82 to 13.0	9.9 titers Interval 5.39 to 18.0	9.15 titers Interval 4.95 to 17.0
Increase in Serogroup A, C, W-135 and Y Specific hSBA Titers Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup Y - hSBA GMT (N=32,20,15)- after	492 titers Interval 305.0 to 793.0	480 titers Interval 269.0 to 857.0	475 titers Interval 220.0 to 1025.0

SECONDARY outcome

Timeframe: One month after primary vaccination

Population: Analysis was performed on the PP primary population and PP persistence population, subjects lacking hSBA ≥1:8 one month after primary vaccination.

The memory B cell response in children lacking a hSBA titer ≥1:8 one month after MenACWY-CRM primary vaccination was calculated as the mean number of meningococcal serogroup specific memory B cells, measured by ELISpot assay per 2x100000 LOC.

Outcome measures

Outcome measures
Measure	MenACWY-CRM and Routine Vaccines (Group 1) n=88 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) n=34 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) n=50 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Serogroups A, C, W-135 and Y Specific Memory B Cell Response in Children Lacking a hSBA Titer of ≥1:8 One Month After MenACWY-CRM Primary Vaccination Serogroup A specific memory B cells (N=24,11,8)	1.533 B cells per 2x100000 lymphocytes Standard Deviation 1.028	1.391 B cells per 2x100000 lymphocytes Standard Deviation 0.467	1.250 B cells per 2x100000 lymphocytes Standard Deviation 0.000
Serogroups A, C, W-135 and Y Specific Memory B Cell Response in Children Lacking a hSBA Titer of ≥1:8 One Month After MenACWY-CRM Primary Vaccination Serogroup Y specific memory B cells (N=0,1,1)	NA B cells per 2x100000 lymphocytes Standard Deviation NA None of the subject had hSBA titer \<1:8	1.250 B cells per 2x100000 lymphocytes Standard Deviation 0.000	1.250 B cells per 2x100000 lymphocytes Standard Deviation 0.000
Serogroups A, C, W-135 and Y Specific Memory B Cell Response in Children Lacking a hSBA Titer of ≥1:8 One Month After MenACWY-CRM Primary Vaccination Serogroup C specific memory B cells (N=6,2,1)	2.667 B cells per 2x100000 lymphocytes Standard Deviation 2.444	1.250 B cells per 2x100000 lymphocytes Standard Deviation 0.000	1.250 B cells per 2x100000 lymphocytes Standard Deviation NA Analysis was done on one subject only
Serogroups A, C, W-135 and Y Specific Memory B Cell Response in Children Lacking a hSBA Titer of ≥1:8 One Month After MenACWY-CRM Primary Vaccination Serogroup W-135 specific memory B cells (N=3,0,1)	1.250 B cells per 2x100000 lymphocytes Standard Deviation 0.000	NA B cells per 2x100000 lymphocytes Standard Deviation NA None of the subject had hSBA titer \<1:8	1.250 B cells per 2x100000 lymphocytes Standard Deviation NA Analysis was done on one subject only

SECONDARY outcome

Timeframe: Day 0, 7, 14, 49, 90, and 120 after MenACWY-CRM vaccination at month 4

Population: This outcome was assessed in Group 1 PP set population.

To assess the kinetics of serogroup A, C, W-135 and Y specific memory B cells, plasma B cells and IgG concentrations were measured on days 0, 7, 14, 49, 90, and 120 following vaccination with MenACWY-CRM vaccination at month 4 of the study. The memory B cell response at different timepoint was defined as the mean number of meningococcal serogroup A, C, W-135 and Y specific memory B cells, measured in vitro by ELISpot assay per 2x100000 lymphocytes obtained from culture (LOC) of peripheral blood mononuclear cells (PBMC) circulating in blood incubated for 5.5 days in the presence of polyclonal B cell activators in vitro. The B plasma cell response at each time point was defined as the mean number of cells secreting antibodies specific for meningococcal serogroup A, C, W-135 and Y, measured by ELISpot assay, per 2x100000 PBMC.

Outcome measures

Outcome measures
Measure	MenACWY-CRM and Routine Vaccines (Group 1) n=88 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup A sp. memory B cell (N=4)- Day 0	1.25 per 2x100000 cells Standard Deviation 0	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup A sp. memory B cell (N=14)- Day 7	3.889 per 2x100000 cells Standard Deviation 5.07	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup A sp. memory B cell (N=7)- Day 14	2.343 per 2x100000 cells Standard Deviation 2.891	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup A sp. memory B cell (N=10)- Day 49	1.97 per 2x100000 cells Standard Deviation 1.533	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup A sp. memory B cell (N=9)- Day 90	1.25 per 2x100000 cells Standard Deviation 0	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup A sp. memory B cell (N=11)- Day 120	1.845 per 2x100000 cells Standard Deviation 1.14	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup C sp. memory B cell (N=6)- Day 0	1.558 per 2x100000 cells Standard Deviation 0.775	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup C sp. memory B cell (N=16)- Day 7	2.856 per 2x100000 cells Standard Deviation 2.974	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup C sp. memory B cell (N=12)- Day 14	5.183 per 2x100000 cells Standard Deviation 5.723	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup C sp. memory B cell (N=13)- Day 49	2.323 per 2x100000 cells Standard Deviation 2.044	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup C sp. memory B cell (N=16)- Day 90	2.469 per 2x100000 cells Standard Deviation 1.865	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup C sp. memory B cell (N=14)- Day 120	1.561 per 2x100000 cells Standard Deviation 1.163	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup W-135 sp. memory B cell (N=4)- Day 0	1.25 per 2x100000 cells Standard Deviation 0	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup W-135 sp. memory B cell (N=15)- Day 7	3.737 per 2x100000 cells Standard Deviation 6.68	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup W-135 sp. memory B cell (N=12)- Day 14	2.754 per 2x100000 cells Standard Deviation 2.245	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup W-135 sp. memory B cell (N=13)- Day 49	2.735 per 2x100000 cells Standard Deviation 2.4	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup W-135 sp. memory B cell (N=14)- Day 90	1.404 per 2x100000 cells Standard Deviation 0.575	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup W-135 sp. memory B cell (N=14)- Day 120	1.25 per 2x100000 cells Standard Deviation 0	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup Y sp. memory B cell (N=3)- Day 0	1.25 per 2x100000 cells Standard Deviation 0	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup Y sp. memory B cell (N=15)- Day 7	4.847 per 2x100000 cells Standard Deviation 9.043	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup Y sp. memory B cell (N=7)- Day 14	1.471 per 2x100000 cells Standard Deviation 0.586	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup Y sp. memory B cell (N=11)- Day 49	1.482 per 2x100000 cells Standard Deviation 0.769	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup Y sp. memory B cell (N=12)- Day 90	1.567 per 2x100000 cells Standard Deviation 0.74	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup Y sp. memory B cell (N=13)- Day 120	1.527 per 2x100000 cells Standard Deviation 0.684	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup A sp. plasma B cell (N=3)- Day 0	1.25 per 2x100000 cells Standard Deviation 0	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup A sp. plasma B cell (N=1)- Day 7	1.25 per 2x100000 cells Standard Deviation NA Only one subject was analyzed.	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup A sp. plasma B cell (N=1)- Day 14	1.25 per 2x100000 cells Standard Deviation NA Only one subject was analyzed.	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup A sp. plasma B cell (N=2)- Day 49	1.25 per 2x100000 cells Standard Deviation 0	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup A sp. plasma B cell (N=2)- Day 90	1.25 per 2x100000 cells Standard Deviation 0	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup A sp. plasma B cell (N=2)- Day 120	1.25 per 2x100000 cells Standard Deviation 0	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup C sp. plasma B cell (N=3)- Day 0	1.25 per 2x100000 cells Standard Deviation 0	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup C sp. plasma B cell (N=2)- Day 7	2.025 per 2x100000 cells Standard Deviation 1.096	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup C sp. plasma B cell (N=1)- Day 14	1.25 per 2x100000 cells Standard Deviation NA Only one subject was analyzed.	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup C sp. plasma B cell (N=2)- Day 49	1.25 per 2x100000 cells Standard Deviation 0	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup C sp. plasma B cell (N=2)- Day 90	1.25 per 2x100000 cells Standard Deviation 0	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup C sp. plasma B cell (N=3)- Day 120	1.25 per 2x100000 cells Standard Deviation 0	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup W-135 sp. plasma B cell (N=3)- Day 0	1.25 per 2x100000 cells Standard Deviation 0	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup W-135 sp. plasma B cell (N=1)- Day 7	1.25 per 2x100000 cells Standard Deviation NA Only one subject was analyzed.	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup W-135 sp. plasma B cell (N=1)- Day 14	1.25 per 2x100000 cells Standard Deviation NA Only one subject was analyzed.	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup W-135 sp. plasma B cell (N=2)- Day 49	1.25 per 2x100000 cells Standard Deviation 0	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup W-135 sp. plasma B cell (N=2)- Day 90	1.25 per 2x100000 cells Standard Deviation 0	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup W-135 sp. plasma B cell (N=3)- Day 120	1.25 per 2x100000 cells Standard Deviation 0	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup Y sp. plasma B cell (N=3)- Day 0	1.25 per 2x100000 cells Standard Deviation 0	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup Y sp. plasma B cell (N=1)- Day 7	1.25 per 2x100000 cells Standard Deviation NA Only one subject was analyzed.	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup Y sp. plasma B cell (N=1)- Day 14	1.25 per 2x100000 cells Standard Deviation NA Only one subject was analyzed.	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup Y sp. plasma B cell (N=2)- Day 49	1.25 per 2x100000 cells Standard Deviation 0	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup Y sp. plasma B cell (N=2)- Day 90	1.25 per 2x100000 cells Standard Deviation 0	—	—
Serogroup A, C, W-135 and Y Specific Memory B Cells and Plasma B Cells After MenACWY-CRM Primary Vaccination Serogroup Y sp. plasma B cell (N=2)- Day 120	1.25 per 2x100000 cells Standard Deviation 0	—	—

SECONDARY outcome

Timeframe: Day 0, 7, 14, 30, 49, 90,120 after MenACWY-CRM vaccination at month 4

Population: This outcome was assessed in Group 1 PP set population.

To assess the kinetics of serogroup A, C, W-135 and Y specific hSBA titers, the geometric mean titer was measured on day 0, 7, 14, 30, 49, 90, and 120 following vaccination with MenACWY-CRM vaccination at month 4 of the study.

Outcome measures

Outcome measures
Measure	MenACWY-CRM and Routine Vaccines (Group 1) n=88 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup A - hSBA GMTs (N=7)- Day 0	2 titers Interval 2.0 to 2.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup A - hSBA GMTs (N=18)- Day 7	13 titers Interval 7.15 to 25.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup A - hSBA GMTs (N=16)- Day 14	26 titers Interval 10.0 to 63.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup A - hSBA GMTs - Day 30	9.79 titers Interval 7.22 to 13.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup A - hSBA GMTs (N=16)- Day 49	9.53 titers Interval 4.49 to 20.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup A - hSBA GMTs (N=18)- Day 90	2.63 titers Interval 1.77 to 3.91	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup A - hSBA GMTs (N=16)- Day 120	4.45 titers Interval 2.25 to 8.83	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup C - hSBA GMTs (N=5)- Day 0	7.19 titers Interval 1.33 to 39.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup C - hSBA GMTs (N=16)- Day 7	138 titers Interval 43.0 to 439.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup C - hSBA GMTs (N=12)- Day 14	180 titers Interval 55.0 to 596.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup C - hSBA GMTs (N=31)- Day 30	105 titers Interval 73.0 to 151.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup C - hSBA GMTs (N=16)- Day 49	104 titers Interval 50.0 to 219.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup C - hSBA GMTs (N=18)- Day 90	31 titers Interval 18.0 to 53.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup C - hSBA GMTs (N=16)- Day 120	15 titers Interval 6.5 to 36.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup W-135 - hSBA GMTs (N=5)- Day 0	4.43 titers Interval 1.48 to 13.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup W-135 - hSBA GMTs (N=12)- Day 7	99 titers Interval 42.0 to 232.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup W-135 - hSBA GMTs (N=9)- Day 14	144 titers Interval 42.0 to 497.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup W-135 - hSBA GMTs (N=61)- Day 30	60 titers Interval 44.0 to 83.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup W-135 - hSBA GMTs (N=11)- Day 49	35 titers Interval 18.0 to 69.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup W-135 - hSBA GMTs (N=15)- Day 90	20 titers Interval 11.0 to 35.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup W-135 - hSBA GMTs (N=4)- Day 120	12 titers Interval 7.58 to 20.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup Y - hSBA GMTs (N=1)- Day 0	2 titers Only one subject was analyzed.	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup Y - hSBA GMTs (N=8)- Day 7	32 titers Interval 8.06 to 123.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup Y - hSBA GMTs (N=4)- Day 14	95 titers Interval 8.0 to 1131.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup Y - hSBA GMTs (N=20)- Day 30	24 titers Interval 16.0 to 38.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup Y - hSBA GMTs (N=8)- Day 49	33 titers Interval 11.0 to 101.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup Y - hSBA GMTs (N=9)- Day 90	12 titers Interval 4.62 to 29.0	—	—
Serogroup A, C, W-135 and Y Specific hSBA Titers After MenACWY-CRM Primary Vaccination Serogroup Y - hSBA GMTs (N=8)- Day 120	8.15 titers Interval 3.77 to 18.0	—	—

SECONDARY outcome

Timeframe: Day 1 (IgG) and one month after primary vaccination (B cells)

Population: Analysis was performed on the PP primary population.

The serogroup A, C, W-135 and Y specific IgG concentrations were measured in the serum of mothers at the time of their enrollment into the study (Day 1) by ELISA.

Outcome measures

Outcome measures
Measure	MenACWY-CRM and Routine Vaccines (Group 1) n=88 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) n=34 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) n=50 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Correlation and Linear Regression Coefficients Between Serogroup A, C, W-135 and Y Specific Memory B Cells 1 Month After MenACWY-CRM Primary Vaccination and IgG Concentration at Day 1 in the Serum of Mothers of Infants	NA (NUMBER) Outcomes are based on correlation and regression coefficients.	NA (NUMBER) Outcomes are based on correlation and regression coefficients.	NA (NUMBER) Outcomes are based on correlation and regression coefficients.

SECONDARY outcome

Timeframe: 1 month post primary vaccination (B cells) and 12 months (hSBA titers and IgG)

Population: Analysis was performed on the PP dataset of persistence population.

Linear regression analysis between memory B cells at 5 months of age and hSBA titers and IgG at 12 months of age was performed with and without inclusion of demographic factors (subject's household smoking status, number of older children living in subject's household, attendance at daycare and total duration of breast feeding) in the model.

Outcome measures

Outcome measures
Measure	MenACWY-CRM and Routine Vaccines (Group 1) n=79 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) n=37 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) n=39 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Linear Regression Coefficients (1) Between Serogroup A, C, W-135 and Y Memory B at 5 Months and hSBA Titers at 12 Months, (2) Between Serogroup A, C, W-135 and Y Memory B at 5 Months and IgG at 12 Months, After a 2-Dose Primary Course of MenACWY-CRM	NA (NUMBER) Outcomes are based on regression coefficient.	NA (NUMBER) Outcomes are based on regression coefficient.	NA (NUMBER) Outcomes are based on regression coefficient.

SECONDARY outcome

Timeframe: 1 month post primary vaccination (B cells) and 12 months (hSBA titers and IgG)

Population: Analysis was performed on the PP dataset after booster vaccination.

The rise in serogroup-specific hSBA and IgG was calculated by pre/post third dose geometric mean ratios, calculated by the difference in the log10 of the concentrations/titers measured at 13 months to the log10 of the concentrations at 12 months: i.e. rise = log10(x) at 13 months minus log10(x) at 12 months where x is the serogroup specific IgG or SBA titers. Linear regression analysis between memory B cells at 5 months of age and rise in hSBA titers or IgG at 12 months of age was performed with and without inclusion of demographic factors (subject's household smoking status, number of older children living in subject's household, attendance at daycare and total duration of breast feeding) in the model.

Outcome measures

Outcome measures
Measure	MenACWY-CRM and Routine Vaccines (Group 1) n=85 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) n=40 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) n=42 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Linear Regression Coefficients (1) Between Serogroup A, C, W-135 and Y Memory B Cells at 5 Months and Rise in hSBA Titers, (2) Between Serogroup A, C, W-135 and Y Memory B Cells at 5 Months and Rise in IgG, After Third Dose of MenACWY-CRM at 12 Months	NA (NUMBER) Outcomes are based on linear regression coefficient.	NA (NUMBER) Outcomes are based on linear regression coefficient.	NA (NUMBER) Outcomes are based on linear regression coefficient.

SECONDARY outcome

Timeframe: 7 days post each MenACWY-CRM and routine infant vaccination

Population: The analysis was performed on the Safety Population.

Safety was assessed as the percentage of subjects who reported injection site local reactions during 7-day follow-up period after each MenACWY-CRM and routine infant vaccination administered as a primary course of vaccination.

Outcome measures

Outcome measures
Measure	MenACWY-CRM and Routine Vaccines (Group 1) n=108 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) n=54 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) n=54 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. Induration - MenACWY-CRM (Vaccination 1)	35 Percentage of subjects	37 Percentage of subjects	39 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. Tenderness - MenACWY-CRM (Vaccination 1)	32 Percentage of subjects	35 Percentage of subjects	22 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. Tenderness - MenACWY-CRM (Vaccination 2)	19 Percentage of subjects	28 Percentage of subjects	17 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. Erythema - MenACWY-CRM (Vaccination 1)	94 Percentage of subjects	96 Percentage of subjects	94 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. Erythema - MenACWY-CRM (Vaccination 2)	96 Percentage of subjects	96 Percentage of subjects	100 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. Induration - MenACWY-CRM (Vaccination 2)	44 Percentage of subjects	50 Percentage of subjects	54 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. Tenderness - DTaP-IPV-Hib (Vaccination 1)	40 Percentage of subjects	43 Percentage of subjects	28 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. Tenderness - DTaP-IPV-Hib (Vaccination 2)	31 Percentage of subjects	35 Percentage of subjects	31 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. Tenderness - DTaP-IPV-Hib (Vaccination 3)	27 Percentage of subjects	33 Percentage of subjects	24 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. Erythema - DTaP-IPV-Hib (Vaccination 1)	97 Percentage of subjects	98 Percentage of subjects	91 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. Erythema - DTaP-IPV-Hib (Vaccination 2)	94 Percentage of subjects	93 Percentage of subjects	100 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. Erythema - DTaP-IPV-Hib (Vaccination 3)	97 Percentage of subjects	98 Percentage of subjects	98 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. Induration - DTaP-IPV-Hib (Vaccination 1)	49 Percentage of subjects	50 Percentage of subjects	54 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. Induration - DTaP-IPV-Hib (Vaccination 2)	53 Percentage of subjects	65 Percentage of subjects	54 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. Induration - DTaP-IPV-Hib (Vaccination 3)	66 Percentage of subjects	72 Percentage of subjects	70 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. Tenderness - PCV (Vaccination 1)	40 Percentage of subjects	39 Percentage of subjects	33 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. Tenderness - PCV (Vaccination 2)	27 Percentage of subjects	39 Percentage of subjects	26 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. Erythema - PCV (Vaccination 1)	95 Percentage of subjects	98 Percentage of subjects	93 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. Erythema - PCV (Vaccination 2)	97 Percentage of subjects	96 Percentage of subjects	100 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. Induration - PCV (Vaccination 1)	38 Percentage of subjects	44 Percentage of subjects	50 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After Each MenACWY-CRM and Routine Infant Vaccinations. Induration - PCV (Vaccination 2)	53 Percentage of subjects	61 Percentage of subjects	65 Percentage of subjects

SECONDARY outcome

Timeframe: 7 days post vaccination at 2, 3, and 4 months of age

Population: The analysis was performed on the safety population.

Safety was assessed as the percentage of subjects who reported systemic reactions during 7-day follow-up period after MenACWY-CRM (2 and 4 months) and routine infant primary vaccinations (2, 3 and 4 months).

Outcome measures

Outcome measures
Measure	MenACWY-CRM and Routine Vaccines (Group 1) n=108 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) n=54 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) n=54 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Analg. Antipyr. Med. Used (Vaccination 3)	41 Percentage of subjects	33 Percentage of subjects	56 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Vomiting (Vaccination 3)	15 Percentage of subjects	11 Percentage of subjects	15 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Diarrhea (Vaccination 1)	20 Percentage of subjects	20 Percentage of subjects	15 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Diarrhea (Vaccination 2)	17 Percentage of subjects	9 Percentage of subjects	13 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Diarrhea (Vaccination 3)	9 Percentage of subjects	17 Percentage of subjects	13 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Irritability (Vaccination 1)	66 Percentage of subjects	69 Percentage of subjects	61 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Irritability (Vaccination 2)	47 Percentage of subjects	76 Percentage of subjects	50 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Irritability (Vaccination 3)	51 Percentage of subjects	56 Percentage of subjects	57 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Unusual crying (Vaccination 1)	27 Percentage of subjects	20 Percentage of subjects	15 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Unusual crying (Vaccination 2)	17 Percentage of subjects	28 Percentage of subjects	19 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Unusual crying (Vaccination 3)	21 Percentage of subjects	15 Percentage of subjects	26 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Fever (≥38 °C) - Vaccination 1	4 Percentage of subjects	4 Percentage of subjects	0 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Fever (≥38 °C) - Vaccination 2	6 Percentage of subjects	6 Percentage of subjects	0 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Fever (≥38 °C) - Vaccination 3	6 Percentage of subjects	9 Percentage of subjects	4 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Analg. Antipyr. Med. Used (Vaccination 1)	40 Percentage of subjects	26 Percentage of subjects	28 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Analg. Antipyr. Med. Used (Vaccination 2)	26 Percentage of subjects	44 Percentage of subjects	39 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Change in eat. habits (N=106,54,54)- Vaccination 1	19 Percentage of subjects	20 Percentage of subjects	30 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Change in eat. habits (N=107,53,54)- Vaccination 2	18 Percentage of subjects	15 Percentage of subjects	17 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Change in eat. habits (N=106,54,53)- Vaccination 3	19 Percentage of subjects	26 Percentage of subjects	30 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Sleepiness (Vaccination 1)	58 Percentage of subjects	54 Percentage of subjects	59 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Sleepiness (Vaccination 2)	39 Percentage of subjects	33 Percentage of subjects	52 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Sleepiness (Vaccination 3)	35 Percentage of subjects	33 Percentage of subjects	37 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Vomiting (Vaccination 1)	24 Percentage of subjects	11 Percentage of subjects	17 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and Routine Infants Primary Vaccinations Vomiting (Vaccination 2)	14 Percentage of subjects	13 Percentage of subjects	6 Percentage of subjects

SECONDARY outcome

Timeframe: 7 days post 12 month vaccination

Population: The analysis was performed on safety after booster population (safety population who received vaccination at 12 months of age).

Safety was assessed as the percentage of subjects who reported injection site local reactions during 7-day follow-up period after MenACWY-CRM and PCV vaccinations at 12 months of age.

Outcome measures

Outcome measures
Measure	MenACWY-CRM and Routine Vaccines (Group 1) n=103 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) n=50 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) n=52 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Percentage of Subjects Who Reported Injection Site Local Reactions After MenACWY-CRM and PCV Vaccinations at 12 Months of Age Tenderness - MenACWY-CRM	28 Percentage of subjects	28 Percentage of subjects	19 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After MenACWY-CRM and PCV Vaccinations at 12 Months of Age Erythema - MenACWY-CRM	99 Percentage of subjects	92 Percentage of subjects	94 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After MenACWY-CRM and PCV Vaccinations at 12 Months of Age Induration - MenACWY-CRM	52 Percentage of subjects	50 Percentage of subjects	56 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After MenACWY-CRM and PCV Vaccinations at 12 Months of Age Tenderness - PCV	0 Percentage of subjects	30 Percentage of subjects	21 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After MenACWY-CRM and PCV Vaccinations at 12 Months of Age Erythema - PCV	0 Percentage of subjects	86 Percentage of subjects	94 Percentage of subjects
Percentage of Subjects Who Reported Injection Site Local Reactions After MenACWY-CRM and PCV Vaccinations at 12 Months of Age Induration - PCV	0 Percentage of subjects	48 Percentage of subjects	63 Percentage of subjects

SECONDARY outcome

Timeframe: 7 days post 12 months vaccination

Population: The analysis was performed on safety after booster population (safety population who received vaccination at 12 months of age).

Safety was assessed as the percentage of subjects who reported systemic reactions during 7-day follow-up period after MenACWY-CRM and PCV vaccination at 12 months of age.

Outcome measures

Outcome measures
Measure	MenACWY-CRM and Routine Vaccines (Group 1) n=103 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) n=50 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) n=52 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and PCV Vaccination at 12 Months of Age Change in eating habits (N=97,48,52)	23 Percentage of subjects	23 Percentage of subjects	31 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and PCV Vaccination at 12 Months of Age Sleepiness	20 Percentage of subjects	24 Percentage of subjects	25 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and PCV Vaccination at 12 Months of Age Vomiting	3 Percentage of subjects	10 Percentage of subjects	12 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and PCV Vaccination at 12 Months of Age Diarrhea	14 Percentage of subjects	16 Percentage of subjects	15 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and PCV Vaccination at 12 Months of Age Irritability	25 Percentage of subjects	46 Percentage of subjects	40 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and PCV Vaccination at 12 Months of Age Unusual crying	12 Percentage of subjects	20 Percentage of subjects	15 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and PCV Vaccination at 12 Months of Age Fever (≥38 °C)	8 Percentage of subjects	6 Percentage of subjects	6 Percentage of subjects
Percentage of Subjects Who Reported Solicited Systemic Reactions After MenACWY-CRM and PCV Vaccination at 12 Months of Age Analgesics Antipyretics Medicine Used	32 Percentage of subjects	44 Percentage of subjects	46 Percentage of subjects

SECONDARY outcome

Timeframe: Before and one month after booster vaccination

Population: Analysis was performed on the PP dataset of booster vaccination.

Serogroup A, C, W-135 and Y specific IgG concentrations were measured before and one month after MenACWY-CRM booster vaccination by ELISA.

Outcome measures

Outcome measures
Measure	MenACWY-CRM and Routine Vaccines (Group 1) n=85 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) n=40 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) n=42 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Increase in Serogroup A, C, W-135 and Y Specific IgG Concentrations Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup A specific IgG (N=49,23,47) before	0.37 µg/mL Interval 0.27 to 0.49	0.33 µg/mL Interval 0.23 to 0.46	0.31 µg/mL Interval 0.23 to 0.42
Increase in Serogroup A, C, W-135 and Y Specific IgG Concentrations Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup A specific IgG (N=66,34,38) after	4.59 µg/mL Interval 3.63 to 5.89	3.5 µg/mL Interval 2.6 to 4.73	5.18 µg/mL Interval 3.84 to 6.99
Increase in Serogroup A, C, W-135 and Y Specific IgG Concentrations Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup C specific IgG (N=55,25,26) before	0.19 µg/mL Interval 0.16 to 0.23	0.18 µg/mL Interval 0.14 to 0.22	0.2 µg/mL Interval 0.15 to 0.28
Increase in Serogroup A, C, W-135 and Y Specific IgG Concentrations Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup C specific IgG (N=59,33,37) after	1.83 µg/mL Interval 1.43 to 2.35	1.67 µg/mL Interval 1.18 to 2.36	2.63 µg/mL Interval 1.87 to 3.7
Increase in Serogroup A, C, W-135 and Y Specific IgG Concentrations Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup W specific IgG (N=55,21,26) before	0.31 µg/mL Interval 0.25 to 0.38	0.35 µg/mL Interval 0.25 to 0.48	0.29 µg/mL Interval 0.2 to 0.43
Increase in Serogroup A, C, W-135 and Y Specific IgG Concentrations Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup W specific IgG (N=56,32,32) after	5.97 µg/mL Interval 4.67 to 7.64	5.37 µg/mL Interval 4.06 to 7.1	5.12 µg/mL Interval 3.5 to 7.5
Increase in Serogroup A, C, W-135 and Y Specific IgG Concentrations Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup Y specific IgG (N=49,21,24) before	0.43 µg/mL Interval 0.34 to 0.55	0.47 µg/mL Interval 0.33 to 0.67	0.37 µg/mL Interval 0.25 to 0.55
Increase in Serogroup A, C, W-135 and Y Specific IgG Concentrations Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone Serogroup Y specific IgG (N=56,31,33) after	6.2 µg/mL Interval 4.77 to 8.05	5.58 µg/mL Interval 4.06 to 7.67	5.75 µg/mL Interval 3.93 to 8.42

SECONDARY outcome

Timeframe: Day 0, 7, 14, 30, 49, 90,120 after MenACWY-CRM vaccination at month 4

Population: This outcome was assessed in Group 1 PP set population.

To assess the kinetics of serogroup A, C, W-135 and Y specific IgG concentrations, the geometric mean concentration was measured on day 0, 7, 14, 30, 49, 90, and 120 following vaccination with MenACWY-CRM vaccination at month 4 of the study.

Outcome measures

Outcome measures
Measure	MenACWY-CRM and Routine Vaccines (Group 1) n=88 Participants Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup Y specific IgG (N=4)- Day 7	1.46 µg/mL Interval 0.24 to 8.99	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup A specific IgG (N=3)- Day 0	0.98 µg/mL Interval 0.0094 to 1.01	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup A specific IgG (N=9)- Day 7	2.23 µg/mL Interval 1.02 to 4.87	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup A specific IgG (N=7)- Day 14	2.27 µg/mL Interval 0.75 to 6.9	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup A specific IgG (N=45)- Day 30	1.29 µg/mL Interval 1.01 to 1.65	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup A specific IgG (N=5)- Day 49	1.39 µg/mL Interval 0.47 to 4.14	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup A specific IgG (N=5)- Day 90	0.94 µg/mL Interval 0.62 to 1.43	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup A specific IgG (N=1)- Day 120	1.03 µg/mL only one subject was analyzed	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup C specific IgG (N=4)- Day 0	0.92 µg/mL Interval 0.19 to 4.35	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup C specific IgG (N=14)- Day 7	1.4 µg/mL Interval 0.85 to 2.28	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup C specific IgG (N=8)- Day 14	1.43 µg/mL Interval 0.76 to 2.7	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup C specific IgG (N=60)- Day 30	0.94 µg/mL Interval 0.77 to 1.14	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup C specific IgG (N=5)- Day 49	1.02 µg/mL Interval 0.28 to 3.69	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup C specific IgG (N=7)- Day 90	0.75 µg/mL Interval 0.46 to 1.23	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup C specific IgG (N=5)- Day 120	0.85 µg/mL Interval 0.26 to 2.75	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup W-135 specific IgG (N=3)- Day 0	0.43 µg/mL Interval 0.0096 to 1.9	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup W-135 specific IgG (N=10)- Day 7	3.75 µg/mL Interval 1.76 to 8.0	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup W-135 specific IgG (N=8)- Day 14	3.77 µg/mL Interval 1.82 to 7.84	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup W-135 specific IgG (N=39)- Day 30	1.53 µg/mL Interval 1.14 to 2.05	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup W-135 specific IgG (N=6)- Day 49	2.58 µg/mL Interval 0.83 to 8.05	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup W-135 specific IgG (N=9)- Day 90	0.81 µg/mL Interval 0.59 to 1.13	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup W-135 specific IgG (N=2)- Day 120	0.57 µg/mL Interval 0.0011 to 3.05	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup Y specific IgG (N=3)- Day 0	0.82 µg/mL Interval 0.039 to 18.0	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup Y specific IgG (N=3)- Day 14	5.04 µg/mL Interval 0.58 to 44.0	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup Y specific IgG (N=33)- Day 30	1.34 µg/mL Interval 1.01 to 1.79	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup Y specific IgG (N=3)- Day 49	2.47 µg/mL Interval 0.24 to 26.0	—	—
Serogroup A, C, W-135 and Y Specific IgG Concentrations After MenACWY-CRM Primary Vaccination Serogroup Y specific IgG (N=2)- Day 90	0.57 µg/mL Interval 0.039 to 8.17	—	—

Adverse Events

MenACWY-CRM and Routine Vaccines (Group 1)

Serious events: 7 serious events

Other events: 108 other events

Deaths: 0 deaths

MenACWY-CRM and Routine Vaccines (Group 2)

Serious events: 4 serious events

Other events: 54 other events

Deaths: 0 deaths

MenACWY-CRM and Routine Vaccines (Group 3)

Serious events: 6 serious events

Other events: 54 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MenACWY-CRM and Routine Vaccines (Group 1) n=108 participants at risk Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 13 months), and 1 dose each of MMR and Hib (booster) at 13 months.	MenACWY-CRM and Routine Vaccines (Group 2) n=54 participants at risk Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months. This group had an additional blood draw at the time of enrollment.	MenACWY-CRM and Routine Vaccines (Group 3) n=54 participants at risk Infants received 2 doses of MenACWY-CRM (at 2 and 4 months) as a primary course of vaccination and third dose (at 12 months) as a booster. Infants also received routine vaccines - 3 doses of DTaP-Hib-IPV (at 2, 3, and 4 months), 3 doses of PCV (at 2, 4, and 12 months), and 1 dose each of MMR and Hib (booster) at 13 months of age. This group had an additional blood draw at 6-7 days after third dose of MenACWY-CRM.
Gastrointestinal disorders Eosinophilic colitis	0.00% 0/108 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	0.00% 0/54 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	1.9% 1/54 • Number of events 1 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.93% 1/108 • Number of events 1 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	0.00% 0/54 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	0.00% 0/54 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.
General disorders Pyrexia	0.00% 0/108 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	0.00% 0/54 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	1.9% 1/54 • Number of events 1 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.
Infections and infestations Bronchiolitis	1.9% 2/108 • Number of events 2 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	1.9% 1/54 • Number of events 1 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	0.00% 0/54 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.
Infections and infestations Cellulitis	0.00% 0/108 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	1.9% 1/54 • Number of events 1 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	0.00% 0/54 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.
Infections and infestations Gastroenteritis	0.00% 0/108 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	0.00% 0/54 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	3.7% 2/54 • Number of events 2 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.
Infections and infestations Lower respiratory tract infection	0.93% 1/108 • Number of events 1 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	1.9% 1/54 • Number of events 1 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	0.00% 0/54 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.
Infections and infestations Viral infection	2.8% 3/108 • Number of events 3 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	0.00% 0/54 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	3.7% 2/54 • Number of events 2 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/108 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	1.9% 1/54 • Number of events 1 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	0.00% 0/54 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.
Injury, poisoning and procedural complications Head injury	0.00% 0/108 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	0.00% 0/54 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	1.9% 1/54 • Number of events 1 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.
Nervous system disorders Febrile convulsion	0.00% 0/108 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	1.9% 1/54 • Number of events 1 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	0.00% 0/54 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.
Respiratory, thoracic and mediastinal disorders Wheezing	0.93% 1/108 • Number of events 1 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	0.00% 0/54 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.	0.00% 0/54 • All the serious adverse events were collected throughout the study (day 1 to 18 months). Other adverse events included solicited local and systemic reactions and non-serious unsolicited adverse events. Solicited local and systemic reactions were collected from day 1 to day 7 after each vaccination. Non-serious unsolicited adverse events were collected from 7 days after each vaccination to the next visit.

Other adverse events

Additional Information

Posting Director

Novartis Vaccines and Diagnostics

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee the terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
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Restriction type: OTHER