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A complete list of the B1971009 and B1971016 trial investigators is provided in the Supplementary Appendix, available at NEJM.org.
Neisseria meningitidis causes invasive meningococcal disease, which occurs predominantly in infants, adolescents, and young adults.1 Patients frequently present with symptoms similar to those of meningitis or septicemia. Death occurs in up to 15% of infected persons,1 and up to 20% of survivors have long-term impairments.2,3
Serogroup B (meningococcal B) accounts for a large proportion of invasive meningococcal disease in the United States, Europe, and other regions.4-8 Capsular polysaccharide-based vaccines can prevent infection with serogroups A, C, W, and Y, but these vaccines are unsuitable for serogroup B disease because the meningococcal B capsular polysaccharide is not immunogenic.9 Vaccines that target the outer-membrane vesicle have effectively controlled epidemics caused by single meningococcal B strains,10,11 but such vaccines are generally ineffective when used against strains other than the targeted strain. Consequently, efforts to develop a meningococcal B vaccine have focused on surface-exposed proteins with the intention of eliciting protective bactericidal antibodies across diverse global invasive strains.
LP2086, a conserved, surface-exposed bacterial lipoprotein that functions as a human complement factor H-binding protein, has been identified as a vaccine target.12 Epidemiologic studies have suggested that a vaccine containing a factor H-binding protein variant from each of the two immunologically distinct protein subfamilies (A and B) protects against diverse, disease-causing meningococcal B strains.13,14 These findings spurred the development of bivalent rLP2086, or MenB-FHbp (Trumenba, Pfizer), which consists of one factor H-binding protein variant from each subfamily. On the basis of data from phase 1 and 2 studies,15-21 MenB-FHbp was the first meningococcal B vaccine licensed in the United States; licensure of 4CMenB (Bexsero, Novartis), the other meningococcal B vaccine available in the United States, followed. The Advisory Committee on Immunization Practices recommends meningococcal B vaccination for at-risk persons 10 years of age and older and recommends that vaccination be considered for persons 16 to 23 years of age for protection against meningococcal B disease.22,23
Large-scale efficacy studies of meningococcal vaccines are challenging owing to the low incidence of disease, which precludes the use of clinical disease outcomes. Because protection against invasive meningococcal disease requires the use of serum bactericidal antibodies against meningococcal capsular polysaccharides or protein antigens,1 vaccine effectiveness is often...