Trial Outcomes & Findings for Analysis of Bone Marrow and Blood B Cell Immune Responses to Influenza Vaccination (NCT NCT02485639)
NCT ID: NCT02485639
Last Updated: 2023-10-24
Results Overview
Blood Immunoglobulin G (IgG) ASC specific for the seasonal influenza vaccine were measured by enzyme-linked immunosorbent spot (ELISPOT) using vaccine-coated plates. Numbers of influenza-specific ASC per million peripheral blood mononuclear cells are reported.
TERMINATED
PHASE4
27 participants
Day 7
2023-10-24
Participant Flow
The following methods were used to recruit participants: traditional flyers posted throughout campus, word of mouth referrals, and social media posts. In addition, listserves, and campus newsletters were also leveraged to expand our participant reach.
Participant milestones
| Measure |
Influenza Virus Vaccine - Inactivated
All study participants received licensed inactivated influenza vaccine intramuscularly (IM) on Day 0.
Influenza Virus Vaccine Inactivated: A synthetic vaccine consisting of three inactivated influenza viruses: two different influenza type A strains and one influenza type B strain. Trivalent influenza vaccine is formulated annually, based on influenza strains projected to be prevalent in the upcoming flu season. All participants received vaccine IM on Day 0.
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|---|---|
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Overall Study
STARTED
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27
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Overall Study
COMPLETED
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11
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Overall Study
NOT COMPLETED
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16
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Reasons for withdrawal
| Measure |
Influenza Virus Vaccine - Inactivated
All study participants received licensed inactivated influenza vaccine intramuscularly (IM) on Day 0.
Influenza Virus Vaccine Inactivated: A synthetic vaccine consisting of three inactivated influenza viruses: two different influenza type A strains and one influenza type B strain. Trivalent influenza vaccine is formulated annually, based on influenza strains projected to be prevalent in the upcoming flu season. All participants received vaccine IM on Day 0.
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Overall Study
8 participants did not complete study. Study halted due to CoronaVIrus Disease COVID-19 pandemic.
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8
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Overall Study
Early termination
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4
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Overall Study
Withdrawal by Subject
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4
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Baseline Characteristics
Analysis of Bone Marrow and Blood B Cell Immune Responses to Influenza Vaccination
Baseline characteristics by cohort
| Measure |
Influenza Virus Vaccine - Inactivated
n=27 Participants
All study participants received licensed inactivated influenza vaccine intramuscularly on Day 0.
Influenza Virus Vaccine Inactivated: A synthetic vaccine consisting of three inactivated influenza viruses: two different influenza type A strains and one influenza type B strain. Trivalent influenza vaccine is formulated annually, based on influenza strains projected to be prevalent in the upcoming flu season. All participants received vaccine IM on Day 0.
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Age, Categorical
<=18 years
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0 Participants
n=5 Participants
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Age, Categorical
Between 18 and 65 years
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27 Participants
n=5 Participants
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Age, Categorical
>=65 years
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0 Participants
n=5 Participants
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Age, Continuous
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27.4 years
n=5 Participants
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Sex: Female, Male
Female
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14 Participants
n=5 Participants
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Sex: Female, Male
Male
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13 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Hispanic or Latino
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0 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Not Hispanic or Latino
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27 Participants
n=5 Participants
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Ethnicity (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Asian
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4 Participants
n=5 Participants
|
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Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Black or African American
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8 Participants
n=5 Participants
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Race (NIH/OMB)
White
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15 Participants
n=5 Participants
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Race (NIH/OMB)
More than one race
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0 Participants
n=5 Participants
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Race (NIH/OMB)
Unknown or Not Reported
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0 Participants
n=5 Participants
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Region of Enrollment
United States
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27 participants
n=5 Participants
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PRIMARY outcome
Timeframe: Day 7Population: Of the 27 donors enrolled in this study, 24 participants were included in this analysis, as one participant withdrew from the study prior to the Day 7 sample collection, one participant had a failed ELISPOT assay/bad plate batch, and for the remaining donor, a sample was not collected at this time-point, as the donor missed their appointment.
Blood Immunoglobulin G (IgG) ASC specific for the seasonal influenza vaccine were measured by enzyme-linked immunosorbent spot (ELISPOT) using vaccine-coated plates. Numbers of influenza-specific ASC per million peripheral blood mononuclear cells are reported.
Outcome measures
| Measure |
Influenza Virus Vaccine - Inactivated
n=24 Participants
All study participants received licensed inactivated influenza vaccine intramuscularly on Day 0.
Influenza Virus Vaccine Inactivated: A synthetic vaccine consisting of three inactivated influenza viruses: two different influenza type A strains and one influenza type B strain. Trivalent influenza vaccine is formulated annually, based on influenza strains projected to be prevalent in the upcoming flu season. All participants received vaccine IM on Day 0.
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|---|---|
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Number of Influenza-specific Antibody Secreting Cells (ASC) Present in the Blood
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284.2 Number of Influenza-specific ASC/million
Interval 81.8 to 501.2
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PRIMARY outcome
Timeframe: Day 0Population: Of the 27 donors enrolled in this study, 15 donors were eligible to have their samples analyzed for this Day 0 time-point outcome measure. 15 participants were analyzed for this time-point outcome measure as due to limited bone marrow yields, as ELISPOT assays were not run on every bone marrow sample. This was the case for 12 of the donors for this time-point outcome measure.
Influenza-specific IgG ASC and total IgG ASC were measured in bone marrow samples by ELISPOT using plates coated with influenza vaccine or total IgG capture antibody. Influenza-specific bone marrow IgG ASC numbers are expressed as a percentage of the total bone marrow IgG ASC number.
Outcome measures
| Measure |
Influenza Virus Vaccine - Inactivated
n=15 Participants
All study participants received licensed inactivated influenza vaccine intramuscularly on Day 0.
Influenza Virus Vaccine Inactivated: A synthetic vaccine consisting of three inactivated influenza viruses: two different influenza type A strains and one influenza type B strain. Trivalent influenza vaccine is formulated annually, based on influenza strains projected to be prevalent in the upcoming flu season. All participants received vaccine IM on Day 0.
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|---|---|
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Number of Influenza-specific Antibody Secreting Cells (ASC) Present in the Bone Marrow
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1.08 Percent of total BM IgG ASC number
Interval 0.79 to 1.71
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PRIMARY outcome
Timeframe: Day 28Population: Of the 27 donors enrolled in this study, 9 donors were eligible to have their samples analyzed for this Day 28 time-point outcome measure. Due to limited bone marrow yields, ELISPOT assays were not run on every bone marrow sample. This was the case for 14 of the donors for this time-point measure. There were two donor/participant withdrawals prior to the Day 28 time-point collection, and two donors were unable to provide a sample, as their lab values were out of range for the bone marrow draw.
Influenza-specific IgG ASC and total IgG ASC were measured in bone marrow samples by ELISPOT using plates coated with influenza vaccine or total IgG capture antibody. Influenza-specific bone marrow IgG ASC numbers are expressed as a percentage of the total bone marrow IgG ASC number.
Outcome measures
| Measure |
Influenza Virus Vaccine - Inactivated
n=9 Participants
All study participants received licensed inactivated influenza vaccine intramuscularly on Day 0.
Influenza Virus Vaccine Inactivated: A synthetic vaccine consisting of three inactivated influenza viruses: two different influenza type A strains and one influenza type B strain. Trivalent influenza vaccine is formulated annually, based on influenza strains projected to be prevalent in the upcoming flu season. All participants received vaccine IM on Day 0.
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Number of Influenza-specific Antibody Secreting Cells (ASC) Present in the Bone Marrow
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3.49 Percent of total BM IgG ASC number
Interval 2.19 to 3.75
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PRIMARY outcome
Timeframe: Day 365Population: Of the 27 donors enrolled in this study, seven donors were eligible to have their samples analyzed for this Day 365 time-point outcome measure. Due to limited bone marrow yields, ELISPOT assays were not run on every bone marrow sample. This was the case for three of the donors for this time-point outcome measure. There were nine donor/participant withdrawals prior to the Day 365 time-point collection. Eight Day 365 visits were halted due to COVID, and samples could not be collected.
Influenza-specific IgG ASC and total IgG ASC were measured in bone marrow samples by ELISPOT using plates coated with influenza vaccine or total IgG capture antibody. Influenza-specific bone marrow IgG ASC numbers are expressed as a percentage of the total bone marrow IgG ASC number.
Outcome measures
| Measure |
Influenza Virus Vaccine - Inactivated
n=7 Participants
All study participants received licensed inactivated influenza vaccine intramuscularly on Day 0.
Influenza Virus Vaccine Inactivated: A synthetic vaccine consisting of three inactivated influenza viruses: two different influenza type A strains and one influenza type B strain. Trivalent influenza vaccine is formulated annually, based on influenza strains projected to be prevalent in the upcoming flu season. All participants received vaccine IM on Day 0.
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Number of Influenza-specific Antibody Secreting Cells (ASC) Present in the Bone Marrow
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1.48 Percent of total BM IgG ASC number
Interval 1.24 to 1.78
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PRIMARY outcome
Timeframe: Day 0Population: Of the 27 donors enrolled in this study, all 27 donors were eligible to have their samples analyzed for this Day 0 time-point outcome measure.
Influenza-specific memory B cells were assayed by ELISPOT after polyclonal stimulation of peripheral blood mononuclear cells to generate ASC. The influenza-specific memory B cell frequencies are reported as the percentage of IgG secreting cells found in the stimulated cultures.
Outcome measures
| Measure |
Influenza Virus Vaccine - Inactivated
n=27 Participants
All study participants received licensed inactivated influenza vaccine intramuscularly on Day 0.
Influenza Virus Vaccine Inactivated: A synthetic vaccine consisting of three inactivated influenza viruses: two different influenza type A strains and one influenza type B strain. Trivalent influenza vaccine is formulated annually, based on influenza strains projected to be prevalent in the upcoming flu season. All participants received vaccine IM on Day 0.
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Number of Influenza-specific Memory B Cells Present in the Blood
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.81 percentage of IgG secreting cells
Interval 0.6 to 1.34
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PRIMARY outcome
Timeframe: Day 28Population: Of the 27 donors enrolled in this study, 25 donors were eligible to have their samples analyzed for this Day 28 time-point outcome measure. There were two donor withdrawals prior to the Day 28 time-point collection.
Influenza-specific memory B cells were assayed by ELISPOT after polyclonal stimulation of peripheral blood mononuclear cells to generate ASC. The influenza-specific memory B cell frequencies are reported as the percentage of IgG secreting cells found in the stimulated cultures.
Outcome measures
| Measure |
Influenza Virus Vaccine - Inactivated
n=25 Participants
All study participants received licensed inactivated influenza vaccine intramuscularly on Day 0.
Influenza Virus Vaccine Inactivated: A synthetic vaccine consisting of three inactivated influenza viruses: two different influenza type A strains and one influenza type B strain. Trivalent influenza vaccine is formulated annually, based on influenza strains projected to be prevalent in the upcoming flu season. All participants received vaccine IM on Day 0.
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|---|---|
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Number of Influenza-specific Memory B Cells Present in the Blood
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2.3 percentage of IgG secreting cells
Interval 1.35 to 4.4
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PRIMARY outcome
Timeframe: Day 365Population: Of the 27 donors enrolled in this study, 10 donors were eligible to have their samples analyzed for this Day 365 time-point outcome measure. There were 9 donor/participant withdrawals prior to the Day 365 time-point collection. COVID halted the Day 365 visits for 8 participants.
Influenza-specific memory B cells were assayed by ELISPOT after polyclonal stimulation of peripheral blood mononuclear cells to generate ASC. The influenza-specific memory B cell frequencies are reported as the percentage of IgG secreting cells found in the stimulated cultures.
Outcome measures
| Measure |
Influenza Virus Vaccine - Inactivated
n=10 Participants
All study participants received licensed inactivated influenza vaccine intramuscularly on Day 0.
Influenza Virus Vaccine Inactivated: A synthetic vaccine consisting of three inactivated influenza viruses: two different influenza type A strains and one influenza type B strain. Trivalent influenza vaccine is formulated annually, based on influenza strains projected to be prevalent in the upcoming flu season. All participants received vaccine IM on Day 0.
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|---|---|
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Number of Influenza-specific Memory B Cells Present in the Blood
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0.82 percentage of IgG secreting cells
Interval 0.49 to 1.49
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PRIMARY outcome
Timeframe: Day 365Population: Many of the participants enrolled in the last season of the study were lost to follow-up for the one year timepoint due to research being halted due to COVID.
Initial seroconversion is defined as having a pre-vaccination (day 0) hemagglutination inhibition (HAI) titer \< 1:40 against a particular strain and a day 28 post-vaccination titer \> / = 1:40 against the same strain OR a pre-vaccination HAI titer \>1:40 and an increase in titer of at least 4-fold on day 28 relative to day 0. Maintenance of seroconversion in those who initially seroconverted is defined as maintaining an HAI titer \>/= 40 at 1 year in those with day 0 titers \< 40 OR maintaining a \>/= 4-fold increase in HAI titer at one year compared to day 0. HAI assays were performed using 0.75% guinea pig red blood cells and virus stocks matched to the strains in the vaccines received by each donor.
Outcome measures
| Measure |
Influenza Virus Vaccine - Inactivated
n=10 Participants
All study participants received licensed inactivated influenza vaccine intramuscularly on Day 0.
Influenza Virus Vaccine Inactivated: A synthetic vaccine consisting of three inactivated influenza viruses: two different influenza type A strains and one influenza type B strain. Trivalent influenza vaccine is formulated annually, based on influenza strains projected to be prevalent in the upcoming flu season. All participants received vaccine IM on Day 0.
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|---|---|
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Number of Subjects Who Initially Seroconverted and Maintained Seroconversion at 1 Year Post Vaccination
H1N1 seroconversion maintenance · never seroconverted
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9 Participants
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Number of Subjects Who Initially Seroconverted and Maintained Seroconversion at 1 Year Post Vaccination
H1N1 seroconversion maintenance · seroconverted at day 28 but seroconversion not maintained at day 365
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1 Participants
|
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Number of Subjects Who Initially Seroconverted and Maintained Seroconversion at 1 Year Post Vaccination
H1N1 seroconversion maintenance · seroconverted at day 28 and maintained seroconversion at day 365
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0 Participants
|
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Number of Subjects Who Initially Seroconverted and Maintained Seroconversion at 1 Year Post Vaccination
H3N2 seroconversion maintenance · never seroconverted
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9 Participants
|
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Number of Subjects Who Initially Seroconverted and Maintained Seroconversion at 1 Year Post Vaccination
H3N2 seroconversion maintenance · seroconverted at day 28 but seroconversion not maintained at day 365
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0 Participants
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Number of Subjects Who Initially Seroconverted and Maintained Seroconversion at 1 Year Post Vaccination
H3N2 seroconversion maintenance · seroconverted at day 28 and maintained seroconversion at day 365
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1 Participants
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Number of Subjects Who Initially Seroconverted and Maintained Seroconversion at 1 Year Post Vaccination
B/Victoria seroconversion maintenance · never seroconverted
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10 Participants
|
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Number of Subjects Who Initially Seroconverted and Maintained Seroconversion at 1 Year Post Vaccination
B/Victoria seroconversion maintenance · seroconverted at day 28 but seroconversion not maintained at day 365
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0 Participants
|
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Number of Subjects Who Initially Seroconverted and Maintained Seroconversion at 1 Year Post Vaccination
B/Victoria seroconversion maintenance · seroconverted at day 28 and maintained seroconversion at day 365
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0 Participants
|
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Number of Subjects Who Initially Seroconverted and Maintained Seroconversion at 1 Year Post Vaccination
B/Yamagata seroconversion maintenance · never seroconverted
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9 Participants
|
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Number of Subjects Who Initially Seroconverted and Maintained Seroconversion at 1 Year Post Vaccination
B/Yamagata seroconversion maintenance · seroconverted at day 28 but seroconversion not maintained at day 365
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0 Participants
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Number of Subjects Who Initially Seroconverted and Maintained Seroconversion at 1 Year Post Vaccination
B/Yamagata seroconversion maintenance · seroconverted at day 28 and maintained seroconversion at day 365
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1 Participants
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PRIMARY outcome
Timeframe: Day 28Seroconversion defined as having a pre-vaccination (day 0) hemagglutination inhibition (HAI) titer \< 1:40 against a particular strain and a Day 28 post-vaccination titer \> / = 1:40 against the same strain OR a pre-vaccination HAI titer \>1:40 and an increase in titer of at least 4-fold on day 28. HAI assays were performed using 0.75% guinea pig red blood cells and virus stocks matched to the strains in the vaccines received by each donor.
Outcome measures
| Measure |
Influenza Virus Vaccine - Inactivated
n=25 Participants
All study participants received licensed inactivated influenza vaccine intramuscularly on Day 0.
Influenza Virus Vaccine Inactivated: A synthetic vaccine consisting of three inactivated influenza viruses: two different influenza type A strains and one influenza type B strain. Trivalent influenza vaccine is formulated annually, based on influenza strains projected to be prevalent in the upcoming flu season. All participants received vaccine IM on Day 0.
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Number of Subjects Achieving Seroconversion to Each of the Strains in the Vaccine
B/Yamagata seroconversion · HAI >/= 1:40 on day 0, < 4-fold HAI increase on day 28 (no seroconversion)
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21 Participants
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Number of Subjects Achieving Seroconversion to Each of the Strains in the Vaccine
H1N1 seroconversion · HAI < 1:40 on day 0, HAI < 1:40 on day 28 (no seroconversion)
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0 Participants
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Number of Subjects Achieving Seroconversion to Each of the Strains in the Vaccine
H1N1 seroconversion · HAI < 1:40 on day 0, HAI >/= 1:40 on day 28 (seroconverted)
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1 Participants
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Number of Subjects Achieving Seroconversion to Each of the Strains in the Vaccine
H1N1 seroconversion · HAI >/= 1:40 on day 0, < 4-fold HAI increase on day 28 (no seroconversion)
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20 Participants
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Number of Subjects Achieving Seroconversion to Each of the Strains in the Vaccine
H1N1 seroconversion · HAI >/= 1:40 on day 0, >/= 4-fold HAI increase on day 28 (seroconverted)
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4 Participants
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Number of Subjects Achieving Seroconversion to Each of the Strains in the Vaccine
H3N2 seroconversion · HAI < 1:40 on day 0, HAI < 1:40 on day 28 (no seroconversion)
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0 Participants
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Number of Subjects Achieving Seroconversion to Each of the Strains in the Vaccine
H3N2 seroconversion · HAI < 1:40 on day 0, HAI >/= 1:40 on day 28 (seroconverted)
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5 Participants
|
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Number of Subjects Achieving Seroconversion to Each of the Strains in the Vaccine
H3N2 seroconversion · HAI >/= 1:40 on day 0, < 4-fold HAI increase on day 28 (no seroconversion)
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15 Participants
|
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Number of Subjects Achieving Seroconversion to Each of the Strains in the Vaccine
H3N2 seroconversion · HAI >/= 1:40 on day 0, >/= 4-fold HAI increase on day 28 (seroconverted)
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5 Participants
|
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Number of Subjects Achieving Seroconversion to Each of the Strains in the Vaccine
B/Victoria seroconversion · HAI < 1:40 on day 0, HAI < 1:40 on day 28 (no seroconversion)
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7 Participants
|
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Number of Subjects Achieving Seroconversion to Each of the Strains in the Vaccine
B/Victoria seroconversion · HAI < 1:40 on day 0, HAI >/= 1:40 on day 28 (seroconverted)
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4 Participants
|
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Number of Subjects Achieving Seroconversion to Each of the Strains in the Vaccine
B/Victoria seroconversion · HAI >/= 1:40 on day 0, < 4-fold HAI increase on day 28 (no seroconversion)
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14 Participants
|
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Number of Subjects Achieving Seroconversion to Each of the Strains in the Vaccine
B/Victoria seroconversion · HAI >/= 1:40 on day 0, >/= 4-fold HAI increase on day 28 (seroconverted)
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0 Participants
|
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Number of Subjects Achieving Seroconversion to Each of the Strains in the Vaccine
B/Yamagata seroconversion · HAI < 1:40 on day 0, HAI < 1:40 on day 28 (no seroconversion)
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0 Participants
|
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Number of Subjects Achieving Seroconversion to Each of the Strains in the Vaccine
B/Yamagata seroconversion · HAI < 1:40 on day 0, HAI >/= 1:40 on day 28 (seroconverted)
|
1 Participants
|
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Number of Subjects Achieving Seroconversion to Each of the Strains in the Vaccine
B/Yamagata seroconversion · HAI >/= 1:40 on day 0, >/= 4-fold HAI increase on day 28 (seroconverted)
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3 Participants
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SECONDARY outcome
Timeframe: Day 7Population: Of the 27 donors enrolled in this study, 19 donors were eligible to have their samples analyzed for this Day 7 time-point outcome measure. There was 1 donor/participant withdrawal prior to the Day 7 time-point collection. Three samples were not able to be used due to a failed assay, a processing error and a missed appointment. Due to limited yields, assays were not performed on four of the samples.
Blood IgG ASC specific for the seasonal influenza vaccine were measured by ELISPOT using plates coated with chimeric hemagglutinin antigen containing the pandemic H1 stem domain fused to the head domain of an H9 influenza virus. Numbers of stem-specific ASC per million peripheral blood mononuclear cells are reported.
Outcome measures
| Measure |
Influenza Virus Vaccine - Inactivated
n=19 Participants
All study participants received licensed inactivated influenza vaccine intramuscularly on Day 0.
Influenza Virus Vaccine Inactivated: A synthetic vaccine consisting of three inactivated influenza viruses: two different influenza type A strains and one influenza type B strain. Trivalent influenza vaccine is formulated annually, based on influenza strains projected to be prevalent in the upcoming flu season. All participants received vaccine IM on Day 0.
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|---|---|
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Frequency of Hemagglutinin Stem Reactive Responses to Influenza Vaccine Among Blood Plasmablasts
|
1.24 Number of stem-specific ASC per mil PBMC
Interval 0.7 to 2.76
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SECONDARY outcome
Timeframe: Day 365Population: This assay was not run due to limited sample quantities.
Influenza-specific IgG ASC and total IgG ASC were measured in bone marrow samples by ELISPOT using plates coated with H9 head/H1 stem chimeric hemagglutinin antigen or total IgG capture antibody. Stem-specific bone marrow IgG ASC numbers are expressed as a percentage of the total bone marrow IgG ASC number.
Outcome measures
Outcome data not reported
Adverse Events
Influenza Virus Vaccine Inactivated
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Influenza Virus Vaccine Inactivated
n=27 participants at risk
All study participants received licensed inactivated influenza vaccine intramuscularly on Day 0.
Influenza Virus Vaccine Inactivated: A synthetic vaccine consisting of three inactivated influenza viruses: two different influenza type A strains and one influenza type B strain. Trivalent influenza vaccine is formulated annually, based on influenza strains projected to be prevalent in the upcoming flu season. All participants received vaccine IM on Day 0.
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|---|---|
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Gastrointestinal disorders
Nausea
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3.7%
1/27 • Number of events 1 • 1 year Adverse event data were collected from Day 0 (enrollment) to Day 365 (the end of follow-up). Adverse event data were collected at each of the follow-up visits (Day 7, Day 14, Day 28, Day 90, and Day 365).
At each of the follow-up visits (Day 7, Day 14, Day 28, Day 90, and Day 365), participants were asked about any adverse events that they might have experienced since their last visit. Clinical health assessments were conducted at every study visit, and included inquiry regarding any illness, any change in medication, and any overall health changes since the last study visit. Adverse event data was collected from enrollment until the end of follow-up at Day 365.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place