Immunogenicity of a Meningococcal B Vaccine during a University Outbreak

Abstract

Backround: In December 2013, a multicomponent meningococcal serogroup B (4CMenB) vaccine was used before licensure on the basis of special consideration by the Food and Drug Administration to respond to an outbreak of Neisseria meningitidis B at a U.S. university. Data suggested that vaccination would control the outbreak because isolates expressed antigens that were closely related to the vaccine antigens (factor H-binding protein [fHbp] and neisserial heparin-binding antigen). We quantified the immune responses induced by 4CMenB during the outbreak.

Methods: We conducted a seroprevalence survey among students to assess vaccination status and collect serum specimens to quantify titers of serum bactericidal antibodies (SBA) with an assay that included human complement (hSBA). We compared the proportion of vaccinated and unvaccinated participants who were seropositive for the outbreak strain and for one closely related reference strain (44/76-SL, which included fHbp) and one mismatched reference strain (5/99, which included neisserial adhesin A), both of which were used in vaccine development. Seropositivity was defined as an hSBA titer of 4 or higher.

Results: Among the 499 participants who received two doses of the 4CMenB vaccine 10 weeks apart, 66.1% (95% confidence interval [CI], 61.8 to 70.3) were seropositive for the outbreak strain, although the geometric mean titer was low at 7.6 (95% CI, 6.7 to 8.5). Among a random subgroup of 61 vaccinees who also received two doses but did not have a detectable protective response to the outbreak strain, 86.9% (95% CI, 75.8 to 94.2) were seropositive for the 44/76-SL strain, for which there was a geometric mean titer of 17.4 (95% CI, 13.0 to 23.2), whereas 100% of these vaccinees (95% CI, 94.1 to 100) were seropositive for the 5/99 strain and had a higher geometric mean titer (256.3; 95% CI, 187.3 to 350.7). The response to the outbreak strain was moderately correlated with the response to the 44/76-SL strain (Pearson's correlation,0.64; P<0.001) but not with the response to the 5/99 strain (Pearson's correlation,-0.06; P=0.43).

Conclusions: Eight weeks after the second dose of the 4CMenB vaccine was administered, there was no evidence of an hSBA response against the outbreak strain in 33.9% of vaccinees, although no cases of meningococcal disease caused by N. meningitidis B were reported among vaccinated students. (Funded by Princeton University and others.).

Figure 1. Relationships among the Timing of Diagnosis, 4CMenB Vaccine Campaigns, and the Seroprevalence Survey

The figure shows the timing of the diagnosis of cases of meningococcal disease associated with the outbreak (with numbers indicating the date of diagnosis), the timing of the 4CMenB vaccination campaigns held at the university (with numbers indicating the days of the month of vaccination), and the timing of the seroprevalence survey (with numbers indicating the dates during which the survey was conducted).

Figure 2. Positive Predictive Value for hSBA Immunity against the Outbreak Strain, According to the 44/76-SL Antibody Titer

The black curve shows the positive predictive value (PPV) of the human serum bactericidal assay (hSBA) for the 44/76-SL reference strain (i.e., the probability that those with a certain hSBA titer against 44/76-SL will be seropositive for the outbreak strain). The orange dashed line shows the proportion of participants with 44/76-SL responses that were greater than or equal to each titer value.