Persisting immune responses indicating long-term protection after booster dose with meningococcal group B outer membrane vesicle vaccine

Abstract

MenBvac is an outer membrane vesicle vaccine against systemic meningococcal disease caused by serogroup B Neisseria meningitidis. In this placebo-controlled double-blind study including 374 healthy adolescents, the safety and immunogenicity of a schedule of three primary doses 6 weeks apart followed by a fourth dose a year later were evaluated. Antibody responses to the vaccine strain and heterologous strains (non-vaccine-type strains) and the persistence of these antibodies were measured by the serum bactericidal assay (SBA) and enzyme-linked immunosorbent assay up to 1 year after the last dose. The proportion of subjects with SBA titers of > or = 4 against the vaccine strain increased from 3% prevaccination to 65% after the third dose. Ten months later, this proportion had declined to 28%. The fourth dose induced a booster response demonstrated by 93% of subjects achieving a titer of > or = 4. One year after the booster dose, 64% still showed SBA titers of > or = 4. Cross-reacting antibodies were induced against all heterologous strains tested, although the magnitude of SBA titers differed widely between the different strains. All four doses of MenBvac were safe. Both MenBvac and the placebo had reactogenicity profiles of mild to moderate local and systemic reactions. Pain, the most common reaction, was reported with similar frequencies in both groups. No serious adverse events occurred in the MenBvac group. This study confirmed the good immunogenicity of the primary course of MenBvac and demonstrated prolonged persistence and increased cross-reactivity of functional antibodies elicited by a booster dose.

FIG. 1.

Subject disposition flow chart. The numbers of subjects (N) receiving MenBvac and placebo, respectively, are presented by dose. For the numbers of samples available for SBA analysis, see the legend to Fig. 2.

FIG. 2.

Proportions of subjects with SBA titers of ≥4 against the vaccine strain before vaccination (pre-vacc.) and at different time points after vaccination in subjects vaccinated with MenBvac and a control group given placebo. In the MenBvac group, serum samples were available for 227 subjects before vaccination, 224 subjects at 6 weeks after the second dose, 218 subjects at 6 weeks after the third dose, 208 subjects at 10 months after the third dose, 202 subjects at 6 weeks after the fourth dose, and 188 subjects at 1 year after the fourth dose. In the placebo group, serum samples were available from 120 subjects before vaccination, 118 subjects at 6 weeks after the second dose, 116 subjects at 6 weeks after the third dose, 109 subjects at 10 months after the third dose, 107 subjects at 6 weeks after the fourth dose, and 94 subjects at one year after the fourth dose. wk, weeks; mo, months.

FIG. 3.

GMTs (SBA) against the vaccine strain before vaccination and at different time points after vaccination for subjects given MenBvac or placebo. Arrows indicate the immunizations. For the number of subjects at each time point, see the legend to Fig. 2.