MenB-FHbp Vaccine Protects Against Diverse Meningococcal Strains in Adolescents and Young Adults: Post Hoc Analysis of Two Phase 3 Studies

摘要

IntroductionTwo phase 3 studies in adolescents and young adults demonstrated that MenB-FHbp, a meningococcal serogroup B (MenB) vaccine, elicits protective immune responses after 2 or 3 doses based on serum bactericidal antibody assays using human complement (hSBA) against 4 primary and 10 additional diverse, vaccine-heterologous MenB test strains. Lower limits of quantitation (LLOQs; titers 1:8 or 1:16; titers?≥?1:4 correlate with protection) were used to evaluate responses to individual strains and all 4 primary strains combined (composite response). A post hoc analysis evaluated percentages of subjects with protective responses to as many as 8 strains combined (4 primary plus additional strains).MethodsImmune responses were measured using hSBAs against 4 primary strains in adolescents ( n =?1509, MenB-FHbp; n =?898, hepatitis A virus vaccine/saline) and young adults ( n =?2480, MenB-FHbp; n =?824, saline) receiving MenB-FHbp or control at 0, 2, and 6?months. Ten additional strains were evaluated in subsets of subjects from approximately 1800 MenB-FHbp recipients across both studies. Percentages of subjects with hSBA titers?≥?LLOQ for different numbers of primary strains or primary plus additional strains combined (7 or 8 strains total per subset) were determined before vaccination, 1?month post-dose 2, and 1?month post-dose 3.ResultsAcross the panel of primary plus additional strains, at 1?month post-dose 3, titers?≥?LLOQ were elicited in 93.7–95.7% of adolescents and 91.7–95.0% of young adults for?≥?5 test strains combined and in 70.5–85.8% of adolescents and 67.5–81.4% of young adults for?≥?7 strains combined. Among adolescents, 99.8%, 99.0%, 92.8%, and 82.7% had titers?≥?LLOQ against at least 1, 2, 3, and all 4 primary strains, respectively; corresponding percentages for young adults were 99.7%, 97.7%, 94.0%, and 84.5%.ConclusionsResults support the ability of MenB-FHbp to provide broad coverage against MenB strains expressing diverse FHbp variants.Trial RegistrationClinicalTrials.gov identifiers NCT01830855, NCT01352845.