Trial Outcomes & Findings for Genomics and Epigenomics of the Elderly Response to Pneumococcal Vaccines (NCT NCT03104075)

NCT ID: NCT03104075

Last Updated: 2025-08-22

Results Overview

To vaccinate healthy older participants with pneumococcal vaccines, collect longitudinal blood samples and assess pneumococcal-specific antibody responses. The unit of measurement used is log2 titer defined as a measure to quantify the overall strength of responses using the sum of all serotype responses. Data shown below is from longitudinal study timepoints (pre and post) first pneumococcal vaccine. At study endpoint, Visit 7, a second pneumococcal vaccine was administered and no further sample collection visits were conducted as proposed in the study design.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 40 participants
• Primary outcome timeframe: 70 days
• Results posted on: 2025-08-22

Participant Flow

Participant milestones

Measure	Prevnar 13 Prevnar 13 (Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein) will be administered at the single 0.5 ml dose, by intramuscular injection with routine clinical care. Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein: One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with Pneumovax 23	Pneumovax 23 Pneumovax 23 (Pneumococcal Vaccine Polyvalent) will be administered at the single 0.5ml dose, by intramuscular injection with routine clinical care. Pneumococcal Vaccine Polyvalent: One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with Prevnar-13
Overall Study STARTED	20	20
Overall Study COMPLETED	19	20
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Measure	Prevnar 13 Prevnar 13 (Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein) will be administered at the single 0.5 ml dose, by intramuscular injection with routine clinical care. Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein: One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with Pneumovax 23	Pneumovax 23 Pneumovax 23 (Pneumococcal Vaccine Polyvalent) will be administered at the single 0.5ml dose, by intramuscular injection with routine clinical care. Pneumococcal Vaccine Polyvalent: One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with Prevnar-13
Overall Study Participant did not complete the last study visit due to hospitalization unrelated to the vaccine	1	0

Baseline Characteristics

Genomics and Epigenomics of the Elderly Response to Pneumococcal Vaccines

Baseline characteristics by cohort

Measure	Prevnar 13 n=19 Participants Prevnar 13 (Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein) will be administered at the single 0.5 ml dose, by intramuscular injection with routine clinical care. Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein: One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with Pneumovax 23	Pneumovax 23 n=20 Participants Pneumovax 23 (Pneumococcal Vaccine Polyvalent) will be administered at the single 0.5ml dose, by intramuscular injection with routine clinical care. Pneumococcal Vaccine Polyvalent: One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with Prevnar-13	Total n=39 Participants Total of all reporting groups
Age, Continuous	67.52 years STANDARD_DEVIATION 7.15 • n=5 Participants	69.25 years STANDARD_DEVIATION 9.25 • n=7 Participants	68.40 years STANDARD_DEVIATION 7.80 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	10 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=5 Participants	20 Participants n=7 Participants	39 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants	19 Participants n=7 Participants	37 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
BMI	24.83 kg/m^2 STANDARD_DEVIATION 3.77 • n=5 Participants	27.16 kg/m^2 STANDARD_DEVIATION 5.94 • n=7 Participants	26.13 kg/m^2 STANDARD_DEVIATION 5.04 • n=5 Participants

PRIMARY outcome

Timeframe: 70 days

Population: 39 healthy volunteers

To vaccinate healthy older participants with pneumococcal vaccines, collect longitudinal blood samples and assess pneumococcal-specific antibody responses. The unit of measurement used is log2 titer defined as a measure to quantify the overall strength of responses using the sum of all serotype responses. Data shown below is from longitudinal study timepoints (pre and post) first pneumococcal vaccine. At study endpoint, Visit 7, a second pneumococcal vaccine was administered and no further sample collection visits were conducted as proposed in the study design.

Outcome measures

Measure	Prevnar 13 n=19 Participants Prevnar 13 (Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein) will be administered at the single 0.5 ml dose, by intramuscular injection with routine clinical care. \[Data analyzed and shown below for the first vaccine i.e. Prevnar 13\] Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein: One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with Pneumovax 23. \[Second vaccine i.e. Pneumovax 23 administered at study endpoint (Visit 7), no further data collected post-second vaccination\]	Pneumovax 23 n=20 Participants Pneumovax 23 (Pneumococcal Vaccine Polyvalent) will be administered at the single 0.5ml dose, by intramuscular injection with routine clinical care. \[Data analyzed and shown below for the first vaccine i.e. Pneumovax 23\] Pneumococcal Vaccine Polyvalent: One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with Prevnar-13. \[Second vaccine i.e. Prevnar 13 administered at study endpoint (Visit 7), no further data collected post-second vaccination\]
Pneumococcal-specific Antibody Responses Baseline	72.1 log2 titer Standard Deviation 19.4	79.4 log2 titer Standard Deviation 18.6
Pneumococcal-specific Antibody Responses Post first vaccination	128.9 log2 titer Standard Deviation 19.5	120.9 log2 titer Standard Deviation 15.0

PRIMARY outcome

Timeframe: 70 days

Population: 39 healthy volunteers

Fold change between the baseline and post first vaccination titers was calculated for each pneumococcal vaccine cohort.

Data shown below is from longitudinal study timepoints (pre and post) first pneumococcal vaccine. At study endpoint, Visit 7, a second pneumococcal vaccine was administered and no further sample collection visits were conducted as proposed in the study design.

Outcome measures

Measure	Prevnar 13 n=19 Participants Prevnar 13 (Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein) will be administered at the single 0.5 ml dose, by intramuscular injection with routine clinical care. \[Data analyzed and shown below for the first vaccine i.e. Prevnar 13\] Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein: One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with Pneumovax 23. \[Second vaccine i.e. Pneumovax 23 administered at study endpoint (Visit 7), no further data collected post-second vaccination\]	Pneumovax 23 n=20 Participants Pneumovax 23 (Pneumococcal Vaccine Polyvalent) will be administered at the single 0.5ml dose, by intramuscular injection with routine clinical care. \[Data analyzed and shown below for the first vaccine i.e. Pneumovax 23\] Pneumococcal Vaccine Polyvalent: One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with Prevnar-13. \[Second vaccine i.e. Prevnar 13 administered at study endpoint (Visit 7), no further data collected post-second vaccination\]
Pneumococcal-specific Antibody Responses - Fold Change Post First Vaccination	55.6 Fold Change Standard Deviation 25.5	41.6 Fold Change Standard Deviation 18.8

SECONDARY outcome

Timeframe: 10 days post first vaccination

Population: To compare the transcriptional responses induced by vaccines on circulating PBMCs we generated RNA-seq data from 31 responders out of 39 total donors. We selected the topmost strong and weak responders from each participant arm (15 participants in Prevnar 13 arm, 16 participants in Pneumovax 23 arm) to generate RNA-seq data. The aim was to identify specific RNA transcriptional signatures of responsivity vs non-responsivity to the first administered pneumococcal vaccine.

RNA-seq and ATAC-seq to enable quantitative assessment of both coding RNA's and ncsRNA's as well as to resolve the epigenetic landscape of immune cells in the context of vaccine responses. We assessed the number of genes upregulated post first vaccination [PCV13 or PPSV23].

Data shown below is from longitudinal study timepoints (pre and post) first pneumococcal vaccine. At study endpoint, Visit 7, a second pneumococcal vaccine was administered and no further sample collection visits were conducted as proposed in the study design.

Outcome measures

Measure	Prevnar 13 n=15 Participants Prevnar 13 (Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein) will be administered at the single 0.5 ml dose, by intramuscular injection with routine clinical care. \[Data analyzed and shown below for the first vaccine i.e. Prevnar 13\] Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein: One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with Pneumovax 23. \[Second vaccine i.e. Pneumovax 23 administered at study endpoint (Visit 7), no further data collected post-second vaccination\]	Pneumovax 23 n=16 Participants Pneumovax 23 (Pneumococcal Vaccine Polyvalent) will be administered at the single 0.5ml dose, by intramuscular injection with routine clinical care. \[Data analyzed and shown below for the first vaccine i.e. Pneumovax 23\] Pneumococcal Vaccine Polyvalent: One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with Prevnar-13. \[Second vaccine i.e. Prevnar 13 administered at study endpoint (Visit 7), no further data collected post-second vaccination\]
Number of Genes Upregulated Following Vaccination With PCV13 or PPSV23	26 Number of upregulated genes at day 10	42 Number of upregulated genes at day 10

SECONDARY outcome

Timeframe: baseline and 10 days post first vaccination

Population: A longitudinal analysis of different cell populations in whole blood samples was performed using flow cytometry at various time points. The number of plasmablasts and ICOS+ Tfh cells at baseline and post first vaccination at day 10 are reported below.

Measure of functional status of immune cells in older participants following administration of a single pneumococcal vaccine, Prevnar13 or Pneumovax23, at baseline and 10 days post first vaccination.

Data shown below is from longitudinal study timepoints (pre and post) first pneumococcal vaccine. At study endpoint, Visit 7, a second pneumococcal vaccine was administered and no further sample collection visits were conducted as proposed in the study design.

Outcome measures

Measure	Prevnar 13 n=19 Participants Prevnar 13 (Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein) will be administered at the single 0.5 ml dose, by intramuscular injection with routine clinical care. \[Data analyzed and shown below for the first vaccine i.e. Prevnar 13\] Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein: One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with Pneumovax 23. \[Second vaccine i.e. Pneumovax 23 administered at study endpoint (Visit 7), no further data collected post-second vaccination\]	Pneumovax 23 n=20 Participants Pneumovax 23 (Pneumococcal Vaccine Polyvalent) will be administered at the single 0.5ml dose, by intramuscular injection with routine clinical care. \[Data analyzed and shown below for the first vaccine i.e. Pneumovax 23\] Pneumococcal Vaccine Polyvalent: One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with Prevnar-13. \[Second vaccine i.e. Prevnar 13 administered at study endpoint (Visit 7), no further data collected post-second vaccination\]
Alterations to APCs, Tfh Cells or B Cells in Response to PCV13 and PPSV23 Plasmablasts cell count at baseline	0.4 cells/microliter Standard Deviation 0.4	0.5 cells/microliter Standard Deviation 0.3
Alterations to APCs, Tfh Cells or B Cells in Response to PCV13 and PPSV23 Plasmablasts cell count at Day 10 post first vaccination	0.7 cells/microliter Standard Deviation 0.8	1.6 cells/microliter Standard Deviation 2.5
Alterations to APCs, Tfh Cells or B Cells in Response to PCV13 and PPSV23 ICOS+Tfh cell count at baseline	4.1 cells/microliter Standard Deviation 3.8	4.1 cells/microliter Standard Deviation 2.4
Alterations to APCs, Tfh Cells or B Cells in Response to PCV13 and PPSV23 ICOS+Tfh cell count at Day 10 post first vaccination	8.8 cells/microliter Standard Deviation 7.6	6.8 cells/microliter Standard Deviation 3.9

Adverse Events

Prevnar 13

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Pneumovax 23

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Prevnar 13 n=19 participants at risk Prevnar 13 (Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein) will be administered at the single 0.5 ml dose, by intramuscular injection with routine clinical care.	Pneumovax 23 n=20 participants at risk Pneumovax 23 (Pneumococcal Vaccine Polyvalent) will be administered at the single 0.5ml dose, by intramuscular injection with routine clinical care.
General disorders Vasovagal Syncope	5.3% 1/19 • Number of events 1 • Data were collected on participants during the 2017-2018 vaccination seasons. Blood samples obtained 7 days prior to vaccination and Day 1, 10, 28, 60 post-vaccination. AEs were collected on participants throughout the duration of the study. None of the AEs were related to the vaccine. One participant had a vasovagal syncope episode due to blood draw.	0.00% 0/20 • Data were collected on participants during the 2017-2018 vaccination seasons. Blood samples obtained 7 days prior to vaccination and Day 1, 10, 28, 60 post-vaccination. AEs were collected on participants throughout the duration of the study. None of the AEs were related to the vaccine. One participant had a vasovagal syncope episode due to blood draw.

Additional Information

Dr. Jacques Banchereau

The Jackson Laboratory

Phone: 860-837-2443

Email: jacques.banchereau@jax.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place