Immunogenicity of 2 Serogroup B Outer-Membrane Protein Meningococcal Vaccines

TLDR

Meningococcal disease is a global health concern, with serogroup B accounting for a substantial proportion of cases, especially in children under four years old. The study aimed to evaluate serum bactericidal activity of serogroup B outer‑membrane protein vaccines against both homologous strains and a heterologous Chilean epidemic strain to assess potential vaccine efficacy. A double‑blind, randomized controlled trial enrolled infants, children, and adults who received three doses of an outer‑membrane protein vaccine (Cuba or Norway) or control, with blood sampled at baseline, before dose three, and 4–6 weeks after dose three. The vaccines elicited strong responses to homologous strains (≥67 % in children/adults, ≥90 % in infants) but only modest responses to the heterologous epidemic strain (31–.

Abstract

ContextMeningococcal disease occurs worldwide, and serogroup B disease accounts for a large proportion of cases. Although persons younger than 4 years are at greatest risk for serogroup B meningococcal disease, vaccine efficacy has not been demonstrated in this age group.ObjectiveTo evaluate serum bactericidal activity (SBA) against homologous vaccine type strains and a heterologous Chilean epidemic strain of Neisseria meningitidis as a potential correlate for vaccine efficacy.DesignDouble-blind, randomized controlled trial conducted between March 14 and July 20, 1994. All blood samples were taken by December 1994.SettingSantiago, Chile, where a clonal serogroup B meningococcal disease epidemic began in 1993.ParticipantsInfants younger than 1 year (n=187), children aged 2 to 4 years (n=183), and adults aged 17 to 30 years (n=173).InterventionParticipants received 3 doses of outer-membrane protein (OMP) meningococcal vaccine developed in either Cuba or Norway or a control vaccine, with each dose given 2 months apart. Blood samples were obtained at baseline, prior to dose 3, and at 4 to 6 weeks after dose 3.Main Outcome MeasureImmune response, defined as a 4-fold or greater rise in SBA titer 4 to 6 weeks after dose 3 compared with prevaccination titer.ResultsChildren and adult recipients of either meningococcal vaccine were more likely than controls to develop an immune response to the heterologous epidemic strain. After 3 doses of vaccine, 31% to 35% of children responded to the vaccine vs 5% to placebo; 37% to 60% of adults responded to vaccine vs 4% to placebo (P<.05 vs control for all). Infants, however, did not respond. In contrast, against homologous vaccine type strains, the response rate was 67% or higher among children and adults and 90% or higher among infants (P<.001 vs control for all). Subsequent SBA against 7 isogenic homologous target strains identified class 1 OMP as the immunodominant antigen.ConclusionsThese data suggest that neither serogroup B OMP meningococcal vaccine would confer protection during a heterologous epidemic. However, epidemic strain–specific vaccines homologous for class 1 OMP are promising candidates for the control of epidemic serogroup B meningococcal disease.