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The protein recruits the complement downregulator, factor H (fH), to the bacterial surface, which enables the organism to resist complement-mediated bacteriolysis. Binding is specific for human fH. In preclinical studies, mice and rabbits immunized with fHbp vaccines developed serum bactericidal antibody responses, which in humans predict protection against developing meningococcal disease. These studies, however, were in animals whose fH did not bind to the vaccine antigen. Here we review the immunogenicity of fHbp vaccines in human fH transgenic mice. The data suggest that animals with high serum human fH concentrations have impaired protective antibody responses. Further, mutant fHbp vaccines with single amino acid substitutions that decrease fH binding are superior immunogens, possibly by unmasking epitopes in the fH binding site that are important for eliciting serum bactericidal antibody responses. Humans immunized with fHbp vaccines develop serum bactericidal antibody, but achieving broad coverage in infants required incorporation of additional antigens, including outer membrane vesicles, which increased rates of fever and local reactions at the injection site. The experimental results in transgenic mice predict that fHbp immunogenicity can be improved in humans by using mutant fHbp vaccines with decreased fH binding. These results have important public health implications for developing improved fHbp vaccines for control of serogroup B meningococcal disease and for development of vaccines against other microbes that bind host molecules.<\/jats:p>","DOI":"10.1128\/cvi.00260-13","type":"journal-article","created":{"date-parts":[[2013,6,6]],"date-time":"2013-06-06T03:57:28Z","timestamp":1370491048000},"page":"1099-1107","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Does Binding of Complement Factor H to the Meningococcal Vaccine Antigen, Factor H Binding Protein, Decrease Protective Serum Antibody Responses?"],"prefix":"10.1128","volume":"20","author":[{"given":"Dan M.","family":"Granoff","sequence":"first","affiliation":[{"name":"Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay","family":"Ram","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter T.","family":"Beernink","sequence":"additional","affiliation":[{"name":"Center for Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1086\/649209","article-title":"Changes in Neisseria meningitidis disease epidemiology in the United States, 1998-2007: implications for prevention of meningococcal disease","volume":"50","author":"Cohn AC","year":"2010","unstructured":"CohnAC MacneilJR HarrisonLH HatcherC TheodoreJ SchmidtM PondoT ArnoldKE BaumbachJ BennettN CraigAS FarleyM GershmanK PetitS LynfieldR ReingoldA SchaffnerW ShuttKA ZellER MayerLW ClarkT StephensD MessonnierNE. 2010. Changes in Neisseria meningitidis disease epidemiology in the United States, 1998-2007: implications for prevention of meningococcal disease. Clin. Infect. Dis. 50:184\u2013191.","journal-title":"Clin. Infect. Dis."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.04.063"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/j.1574-6976.2006.00053.x","article-title":"Vaccination against meningococcal disease in Europe: review and recommendations for the use of conjugate vaccines","volume":"31","author":"Trotter CL","year":"2007","unstructured":"TrotterCL RamsayME. 2007. Vaccination against meningococcal disease in Europe: review and recommendations for the use of conjugate vaccines. FEMS Microbiol. Rev. 31:101\u2013107.","journal-title":"FEMS Microbiol. 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