A Meningococcal Native Outer Membrane Vesicle Vaccine With Attenuated Endotoxin and Overexpressed Factor H Binding Protein Elicits Gonococcal Bactericidal Antibodies
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
2019-03-15Keywords
Neisseria gonorrhoeaeFHbp
NOMV
OMV
gonococcus
meningococcus
vaccine
Bacterial Infections and Mycoses
Immunology of Infectious Disease
Immunoprophylaxis and Therapy
Infectious Disease
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Show full item recordAbstract
BACKGROUND: Meningococcal outer membrane vesicle (OMV) vaccines are prepared with detergents to remove endotoxin, which also remove desirable antigens such as factor H binding protein (FHbp). Native OMV (NOMV) vaccines with genetically attenuated endotoxin do not require detergent treatment and elicit broader serum bactericidal antibody (SBA) responses than OMV or recombinant FHbp (rFHbp) vaccines. METHODS: We measured human complement-mediated SBA responses in mice immunized with NOMV with overexpressed FHbp subfamily B (NOMV-FHbp), NOMV with FHbp genetically inactivated (NOMV-KO), and/or a control rFHbp vaccine against meningococcal and gonococcal strains. RESULTS: Despite having 36-fold less FHbp per dose, the NOMV-FHbp vaccine elicited a > /=3-fold higher serum IgG anti-FHbp geometric mean titer than control vaccines containing rFHbp (P < /= .003). Against 2 meningococcal outbreak strains with mismatched PorA and heterologous FHbp subfamily B sequence variants, the NOMV-FHbp vaccine produced > /=30-fold higher SBA titers than control vaccines. Mice immunized with NOMV-FHbp and NOMV-KO vaccines also elicited SBA against a gonococcal strain (P < .0001 vs the adjuvant-only control group). In contrast, 2 licensed meningococcal serogroup B vaccines, including one containing detergent-extracted OMV, did not produce gonococcal SBA in humans. CONCLUSIONS: A meningococcal NOMV vaccine elicits SBA against gonococci and with overexpressed FHbp elicits SBA against meningococci.Source
Beernink PT, Ispasanie E, Lewis LA, Ram S, Moe GR, Granoff DM. A Meningococcal Native Outer Membrane Vesicle Vaccine With Attenuated Endotoxin and Overexpressed Factor H Binding Protein Elicits Gonococcal Bactericidal Antibodies. J Infect Dis. 2019 Mar 15;219(7):1130-1137. doi: 10.1093/infdis/jiy609. PMID: 30346576; PMCID: PMC6420169. Link to article on publisher's site
DOI
10.1093/infdis/jiy609Permanent Link to this Item
http://hdl.handle.net/20.500.14038/35195PubMed ID
30346576Related Resources
ae974a485f413a2113503eed53cd6c53
10.1093/infdis/jiy609