Abstract
BACKGROUND: 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 220-228 |
| Number of pages | 9 |
| Journal | New England Journal of Medicine |
| Volume | 375 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jul 21 2016 |
Bibliographical note
Funding Information:Funded by Princeton University and others. Supported by grants from the Program on U.S. Health Policy at Princeton University and the Health Grand Challenge at Princeton University (to Dr. Basta), a National Institutes of Health (NIH) Early Independence Award from the Office of the Director (1DP5OD009162, to Dr. Basta), and a grant from the Research and Policy for Infectious Disease Dynamics program of the Science and Technology Directorate of the Department of Homeland Security and the NIH Fogarty International Center (to Drs. Basta and Grenfell). Dr. Johnsen reports receiving travel support from Pfizer; and Drs. Findlow, Bai, and Borrow, performing contract research for GlaxoSmithKline, Novartis, Pfizer, and Sanofi Pasteur on behalf of their institution. No other potential conflict of interest relevant to this article was reported.
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