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

Johannes Beeslaar, Judith Absalon, Annaliesa S Anderson, Joseph J Eiden, Paul Balmer, Shannon L Harris, Thomas R Jones, Robert E O'Neill, Jean-Louis Pregaldien, David Radley, Roger Maansson, John Ginis, Amit Srivastava, John L Perez, Johannes Beeslaar, Judith Absalon, Annaliesa S Anderson, Joseph J Eiden, Paul Balmer, Shannon L Harris, Thomas R Jones, Robert E O'Neill, Jean-Louis Pregaldien, David Radley, Roger Maansson, John Ginis, Amit Srivastava, John L Perez

Abstract

Introduction: Two 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).

Methods: Immune 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.

Results: Across 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%.

Conclusions: Results support the ability of MenB-FHbp to provide broad coverage against MenB strains expressing diverse FHbp variants.

Trial registration: ClinicalTrials.gov identifiers NCT01830855, NCT01352845.

Keywords: Adolescents; Bactericidal activity; Broad coverage; FHbp; MenB-FHbp vaccine; Meningococcal disease; Meningococcal serogroup B; Neisseria meningitidis; Young adults; hSBA.

Figures

Fig. 1
Fig. 1
Percentage of adolescent responders with hSBA titers ≥ LLOQ to different numbers of primary and additional MenB test strains before MenB-FHbp vaccination, 1 month after 2 doses (0, 2 months), and 1 month after 3 doses (0, 2, 6 months). a Subset 1; b subset 2; c subset 3. Evaluation included up to 8 test strains. Subset 1 included the primary test strains (expressing FHbp variants A22, A56, B24, and B44) and additional test strains expressing FHbp variants A15, A19, and A29. Subset 2 included the primary test strains and additional test strains expressing FHbp variants A06, A07, and A12. Subset 3 included the primary test strains and additional test strains expressing FHbp variants B03, B09, B15, and B16. The number of subjects included at each time point is indicated below the x-axis. Fewer subjects were evaluated post-dose 2 than at other time points because of limited supply of qualified assay reagents. FHbp factor H binding protein, hSBA serum bactericidal antibody assay using human complement, LLOQ lower limit of quantitation, MenB Neisseria meningitidis serogroup B. Error bars represent the 95% CIs calculated using the Clopper–Pearson method
Fig. 2
Fig. 2
Percentage of young adult responders with hSBA titers ≥ LLOQ to different numbers of primary and additional MenB test strains before MenB-FHbp vaccination, 1 month after 2 doses (0, 2 months), and 1 month after 3 doses (0, 2, 6 months). a Subset 1; b subset 2; c subset 3. Evaluation included up to 8 test strains. Subset 1 included the primary test strains (expressing FHbp variants A22, A56, B24, and B44) and additional test strains expressing FHbp variants A15, A19, and A29. Subset 2 included the primary test strains and additional test strains expressing FHbp variants A06, A07, and A12. Subset 3 included the primary test strains and additional test strains expressing FHbp variants B03, B09, B15, and B16. The number of subjects included at each time point is indicated below the x-axis. Fewer subjects were evaluated post-dose 2 than at other time points because of limited supply of qualified assay reagents. FHbp factor H binding protein, hSBA serum bactericidal antibody assay using human complement, LLOQ lower limit of quantitation, MenB Neisseria meningitidis serogroup B. Error bars represent the 95% CIs calculated using the Clopper–Pearson method
Fig. 3
Fig. 3
Percentage of adolescents in the a MenB-FHbp and b HAV/saline groups with hSBA titers ≥ LLOQ to different numbers of primary MenB test strains before vaccination, 1 month after 2 doses (0, 2 months), and 1 month after 3 doses (0, 2, 6 months). LLOQ was defined as 1:8 for the test strain expressing FHbp variant A22 and 1:16 for the test strains expressing FHbp variants A56, B24, and B44. The number of subjects included at each time point is indicated below the x-axis. FHbp factor H binding protein, HAV hepatitis A virus vaccine; hSBA serum bactericidal antibody assay using human complement, LLOQ lower limit of quantitation, MenB Neisseria meningitidis serogroup B, MenB-FHbp bivalent rLP2086, Trumenba®. Error bars represent the 95% CIs calculated using the Clopper–Pearson method
Fig. 4
Fig. 4
Percentage of young adults in the a MenB-FHbp and b saline groups with hSBA titers ≥ LLOQ to different numbers of primary MenB test strains before vaccination, 1 month after 2 doses (0, 2 months), and 1 month after 3 doses (0, 2, 6 months). LLOQ was defined as 1:8 for the test strain expressing FHbp variant A22 and 1:16 for the test strains expressing FHbp variants A56, B24, and B44. The number of subjects included at each time point is indicated below the x-axis. FHbp factor H binding protein, hSBA serum bactericidal antibody assay using human complement, LLOQ lower limit of quantitation, MenB Neisseria meningitidis serogroup B, MenB-FHbp bivalent rLP2086, Trumenba®. Error bars represent the 95% CIs calculated using the Clopper–Pearson method

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