Title

A Meningococcal Native Outer Membrane Vesicle Vaccine With Attenuated Endotoxin and Overexpressed Factor H Binding Protein Elicits Gonococcal Bactericidal Antibodies

UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date

2019-03-15

Document Type

Article

Disciplines

Bacterial Infections and Mycoses | Immunology of Infectious Disease | Immunoprophylaxis and Therapy | Infectious Disease

Abstract

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.

Keywords

Neisseria gonorrhoeae, FHbp, NOMV, OMV, gonococcus, meningococcus, vaccine

DOI of Published Version

10.1093/infdis/jiy609

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

Journal/Book/Conference Title

The Journal of infectious diseases

Related Resources

Link to Article in PubMed

PubMed ID

30346576

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