Anti-Factor H Antibody Reactivity in Young Adults Vaccinated with a Meningococcal Serogroup B Vaccine Containing Factor H Binding Protein Kelsey Sharkey, a Peter T. Beernink, a Joanne M. Langley, b Soren Gantt, c Caroline Quach, d Christina Dold, e Qin Liu, f Manuel Galvan, g Dan M. Granoff a a Center for Immunobiology and Vaccine Development, University of California San Francisco Benioff Children’s Hospital Oakland, Oakland, California, USA b IWK Health Centre and the Nova Scotia Health Authority, Canadian Center for Vaccinology at Dalhousie University, Halifax, Nova Scotia, Canada c BC Children’s Hospital Research Institute, Vancouver, British Columbia, Canada d McGill University Health Centre Research Institute and CHU Sainte Justine, Montreal, Quebec, Canada e University of Oxford, Oxford, United Kingdom f Wistar Institute, Philadelphia, Pennsylvania, USA g National Jewish Health Complement Laboratory, Denver, Colorado, USA ABSTRACT Meningococcal serogroup B (MenB) vaccines contain recombinant factor H binding protein (FHbp), which can complex with complement factor H (CFH) and thereby risk eliciting anti-FH autoantibodies. While anti-FH antibodies can be present in sera of healthy persons, the antibodies are implicated in autoimmune atypical he- molytic uremic syndrome and C3 glomerulopathies. We immunized 120 students with a MenB vaccine (Bexsero). By enzyme-linked immunosorbent assay (ELISA), there were small increases in serum anti-FH levels at 3 weeks postvaccination (geo- metric mean optical density at 405 nm [OD 405 ], 0.54 versus 0.51 preimmunization, P  0.003 for each schedule tested). There was a similar small increase in anti-FH an- tibody levels in a second historical MenB study of 20 adults with stored paired pre- immunization and postimmunization sera (P = 0.007) but not in three other studies of 57 adults immunized with other meningococcal vaccines that did not contain re- combinant FHbp (P = 0.17, 0.84, and 0.60, respectively). Thus, humans vaccinated with MenB-4C develop small increases in serum anti-FH antibody reactivity. Al- though not likely to be clinically important, the data indicate a host response to FH. In the prospective MenB study, three subjects (2.5%) developed higher anti-FH titers postimmunization. The elevated titers returned to baseline within 3 to 4 months, and none of the subjects reported adverse events during the follow-up. Although anti-FH antibodies can decrease FH function, the postimmunization sera with high anti-FH antibody levels did not impair serum FH function as measured using a he- molytic assay. Thus, while additional studies are warranted, there is no evidence that the anti-FH antibodies elicited by MenB-4C are likely to cause anti-FH-mediated au- toimmune disorders. (This study has been registered at ClinicalTrials.gov under regis- tration no. NCT02583412.) IMPORTANCE Meningococci are bacteria that cause sepsis and meningitis. Meningo- coccal species are subdivided into serogroups on the basis of different sugar cap- sules. Vaccines that target serogroup A, C, Y, and W capsules are safe and highly ef- fective. New serogroup B (MenB) vaccines target a bacterial protein that can bind to a blood protein called complement factor H (FH). While serogroup B vaccines appear to be safe and effective, there is a theoretical risk that immunization with a bacterial protein that binds host FH might elicit anti-FH autoantibodies. Autoantibodies to FH have been detected in healthy persons but in rare cases can cause certain autoim- mune diseases. We found small and/or transient increases in serum antibody to FH Citation Sharkey K, Beernink PT, Langley JM, Gantt S, Quach C, Dold C, Liu Q, Galvan M, Granoff DM. 2019. Anti-factor H antibody reactivity in young adults vaccinated with a meningococcal serogroup B vaccine containing factor H binding protein. mSphere 4:e00393-19. https://doi.org/10.1128/mSphere .00393-19. Editor Helene F. Rosenberg, National Institute of Allergy and Infectious Diseases Copyright © 2019 Sharkey et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. Address correspondence to Dan M. Granoff, dgranoff@chori.org. Received 30 May 2019 Accepted 18 June 2019 Published RESEARCH ARTICLE Clinical Science and Epidemiology July/August 2019 Volume 4 Issue 4 e00393-19 msphere.asm.org 1 3 July 2019 on June 1, 2020 by guest http://msphere.asm.org/ Downloaded from