Background: 4CMenB has been shown to be immunogenic with an acceptable safety profile in infants and young adolescents. However, no data on long-term persistence after primary vaccination in adolescents are available. This is the first study to assess antibody persistence, booster response, and safety of 4CMenB in adolescents and young adults up to 7.5 years (y) following the primary vaccination in adolescence.
Methods: This phase 3b, open-label, extension study (NCT02446743) assessed the antibody persistence and booster response at 4y (Canada and Australia, NCT01423084) or 7.5y (Chile, NCT00661713) after primary vaccination with 4CMenB (following 0+1-, 0+2-, or 0+6-month [m] schedules), compared with vaccine-naïve (VN), healthy controls. Chilean follow-on (FO) and VN participants aged 1824y received either a booster dose of 4CMenB 7.5y post-primary series (Group FO, N=131) or 2 primary doses, 1m apart (Group VN, N=150). Immunogenicity was measured using human serum bactericidal antibody assay (hSBA) against antigen-specific strains. Immune response was evaluated 1m post-booster vaccination and compared to VN controls at 1m post-first dose. Kinetics of antibody responses were measured at 3, 7, and 30 days (d) post-vaccination. Safety was assessed.
Results: Antibody levels waned at 7.5y post-primary vaccination in Group FO, but were higher than in Group VN at baseline, for all antigens except NHBA (Table). At 1m post-booster/post-first dose, 93100% (Group FO) and 6293% (Group VN) of participants had hSBA titres ≥4; GMTs ranged between 411951 (Group FO) and 9.4346 (Group VN) (Table). The percentages of FO participants with hSBA titres ≥4 remained similar to pre-booster for all 4 antigens at 3d, increased at 7d, and remained unchanged or increased further 30d post-booster. The reactogenicity of 4CMenB was consistent with previous observations in this age group; no safety concerns were identified during the study.
Conclusion: Antibody levels in adolescents and young adults declined at 7.5y after a 2-dose primary series of 4CMenB, but were higher than baseline levels in VN controls. An additional dose of 4CMenB elicited strong anamnestic responses substantially higher than 1 dose in VN controls.
Funding: GlaxoSmithKline Biologicals SA
M. E. Santolaya, None
F. De Looze, GSK: Investigator and Research Contractor , Research grant and Research support .
H. Marshall, Pfizer: Grant Investigator and Investigator , Research grant . GSK: Grant Investigator and Investigator , Research grant .
P. Richmond, GSK: Grant Investigator and Scientific Advisor , Grant recipient .
S. Henein, SKDS Research Inc: Investigator , Research payment .
P. Rheault, None
K. Heaton, Devonshire Clinical Research Inc: Investigator , Research payment .
K. Perrett, None
H. Garfield, None
A. Gupta, None
M. Ferguson, GSK: Investigator , Salary from independent research clinic,CRG .
D. D'Agostino, GSK: Employee , Salary .
D. Toneatto, GSK: Employee and Shareholder , Salary .