Journal
VACCINE
Volume 33, Issue 51, Pages 7168-7175Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2015.10.135
Keywords
Neisseria meningitidis; Vaccine; Complement; Factor H; Factor H binding protein; Non-human primate; 4CMenB; Bexsero (R)
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Funding
- National Institute of Allergy and Infectious Diseases, NIH [R01 AI046464, R01 AI099125, R01 AI114701]
- Office of Research Infrastructure Programs [P51 OD011107]
- National Center for Research Resources, NIH [C06 RR016226]
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FHbp is a major serogroup B meningococcal vaccine antigen. Binding of complement Factor H (FH) to FHbp is specific for human and some non-human primate FH. In previous studies, FH binding to FHbp vaccines impaired protective anti-FHbp antibody responses. In this study we investigated anti-FHbp antibody responses to a third dose of a licensed serogroup B vaccine (MenB-4C) in infant macaques vaccinated in a previous study with MenB-4C. Six macaques with high binding of FH to FHbp (FHhigh), and six with FHlow baseline phenotypes, were immunized three months after dose 2. After dose 2, macaques with the FHlow baseline phenotype had serum anti-FHbp antibodies that enhanced FH binding to FHbp (functionally converting them to a FHhigh phenotype). In this group, activation of the classical complement pathway (C4b deposition) by serum anti-FHbp antibody, and anti-FHbp serum bactericidal titers were lower after dose 3 than after dose 2 (p <0.02). In macaques with the FHhigh baseline phenotype, the respective anti-FHbp C4b deposition and bactericidal titers were similar after doses 2 and 3. Two macaques developed serum anti-FH autoantibodies after dose 2, which were not detected after dose 3. In conclusion, in macaques with the FHlow baseline phenotype whose post-dose 2 serum anti-FHbp antibodies had converted them to FHhigh, the anti-FHbp antibody repertoire to dose 3 was skewed to less protective epitopes than after dose 2. Mutant FHbp vaccines that eliminate FH binding may avoid eliciting anti-FHbp antibodies that enhance FH binding, and confer greater protection with less risk of inducing anti-FH autoantibodies than FHbp vaccines that bind FH. (C) 2015 Elsevier Ltd. All rights reserved.
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