ArticleJournal of immunology (Baltimore, Md. : 1950)2011
A meningococcal factor H binding protein mutant that eliminates factor H binding enhances protective antibody responses to vaccination.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 134 citations in OpenAlex.
- Trial
- Modulation of nasopharyngeal innate defenses by viral coinfection predisposes individuals to experimental pneumococcal carriage.Mucosal immunology · 2016Trial
- Structural insights into zinc piracy by Neisseria gonorrhoeae to overcome nutritional immunity.Structure (London, England : 1993) · 2026Article
- Cloning and expression of natively paired antibody fragments from single B cells of immunized rhesus macaques.Frontiers in immunology · 2026Article
- Structure-based engineering of a nutrient acquisition protein enhances neutralizing antibodies and protection for the development of a gonococcal vaccine.bioRxiv : the preprint server for biology · 2025Article
- Human Factor H and anti-Neisserial surface protein A (NspA) antibodies compete for overlapping binding sites on meningococcal NspA.Infection and immunity · 2025Article
- Rational selection of TbpB variants yields a bivalent vaccine with broad coverage against Neisseria gonorrhoeae.NPJ vaccines · 2025Article
- Factor H binding protein (FHbp): An evaluation of genotypic diversity acrossHuman vaccines & immunotherapeutics · 2024Review
- Investigating the importance of selected surface-exposed loops in HpuB for hemoglobin binding and utilization byInfection and immunity · 2024Article
- Insights into structural vaccinology harnessed for universal coronavirus vaccine development.Clinical and experimental vaccine research · 2024Review
- OpcA and PorB are novel bactericidal antigens of the 4CMenB vaccine in mice and humans.NPJ vaccines · 2023Article
- Point Mutations in TbpA Abrogate Human Transferrin Binding in Neisseria gonorrhoeae.Infection and immunity · 2022Article
- Article
- CspZ FH-Binding Sites as Epitopes Promote Antibody-Mediated Lyme Borreliae Clearance.Infection and immunity · 2022Article
- Article
- Structural characterization of a cross-protective natural chimera of factor H binding protein from meningococcal serogroup B strain NL096.Computational and structural biotechnology journal · 2022Article
- Generation of a Universal Human Complement Source by Large-Scale Depletion of IgG and IgM from Pooled Human Plasma.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Exploring the Ability of Meningococcal Vaccines to Elicit Mucosal Immunity: Insights from Humans and Mice.Pathogens (Basel, Switzerland) · 2021Review
- Two human antibodies to a meningococcal serogroup B vaccine antigen enhance binding of complement Factor H by stabilizing the Factor H binding site.PLoS pathogens · 2021Article
- Human and Veterinary Vaccines for Lyme Disease.Current issues in molecular biology · 2021Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Certain pathogens recruit host complement inhibitors such as factor H (fH) to evade the immune system. Microbial complement inhibitor-binding molecules can be promising vaccine targets by eliciting Abs that neutralize this microbial defense mechanism. One such Ag, meningococcal factor H-binding protein (fHbp), was used in clinical trials before the protein was discovered to bind fH. The potential effect of fH binding on vaccine immunogenicity had not been assessed in experimental animals because fHbp binds human fH specifically. In this study, we developed a human fH transgenic mouse model. Transgenic mice immunized with fHbp vaccine had 4- to 8-fold lower serum bactericidal Ab responses than those of control mice whose native fH did not bind the vaccine. In contrast, Ab responses were unimpaired in transgenic mice immunized with a control meningococcal group C polysaccharide-protein conjugate vaccine. In transgenic mice, immunization with an fH nonbinding mutant of fHbp elicited Abs with higher bactericidal activity than that of fHbp vaccination itself. Abs elicited by the mutant fHbp more effectively blocked fH binding to wild-type fHbp than Abs elicited by fHbp that bound fH. Thus, a mutant fHbp vaccine that does not bind fH but that retains immunogenicity is predicted to be superior in humans to an fHbp vaccine that binds human fH. In the case of mutant fHbp vaccination, the resultant Ab responses may be directed more at epitopes in or near the fH binding site, which result in greater complement-mediated serum bactericidal activity; these epitopes may be obscured when human fH is bound to the wild-type fHbp vaccine.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.