The Neisseria gonorrhoeae Vaccine Candidate NHBA Elicits Antibodies That Are Bactericidal, Opsonophagocytic and That Reduce Gonococcal Adherence to Epithelial Cells.

Evgeny A Semchenko,Christopher J Day,Kate L Seib

doi:10.3390/vaccines8020219

Evgeny A Semchenko, Christopher J Day + Show 1 more

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https://doi.org/10.3390/vaccines8020219

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Journal: Vaccines	Publication Date: May 13, 2020
Citations: 16	License type: CC BY 4.0

Affiliation: Griffith University

Abstract

Due to the continuing emergence of multidrug resistant strains of Neisseria gonorrhoeae there is an urgent need for the development of a gonococcal vaccine. We evaluated the gonococcal Neisseria heparin binding antigen (NHBA) as a potential vaccine candidate, in terms of its sequence conservation and expression in a range of N. gonorrhoeae strains, as well as its immunogenicity and the functional activity of antibodies raised to either the full length NHBA or a C-terminal fragment of NHBA (NHBA-c). The gene encoding NHBA is highly conserved and expressed in all N. gonorrhoeae strains investigated. Recombinant NHBA is immunogenic, and mice immunized with either NHBA or NHBA-c adjuvanted with either Freund’s or aluminium hydroxide (alum) generated a humoral immune response, with predominantly IgG1 antibodies. Antibodies generated by both NHBA and NHBA-c antigens promoted complement activation and mediated bacterial killing via both serum bactericidal activity and opsonophagocytic activity, with slightly higher titers seen for the NHBA-c antigen. Anti-NHBA was also able to block the functional activity of NHBA by reducing binding to heparin and adherence to cervical and urethral epithelial cells. These data suggest that the gonococcal NHBA is a promising vaccine antigen to include in a vaccine to control N. gonorrhoeae.

Highlights

The ongoing emergence of multidrug resistant strains of Neisseria gonorrhoeae is a major challenge to the management of the sexually transmitted infection gonorrhoea [1,2]
We have previously shown that Neisseria heparin binding antigen (NHBA) is conserved in N. gonorrhoeae [12] and here we further examine the sequence variants of NHBA in available gonococcal isolates and genome sequences
A blastn search with the 1281 nucleotide nhba gene from N. gonorrhoeae strain 1291, which encodes the 427 amino acid NHBA (Figure 1a), against the available gonococcal genomes in GenBank revealed that nhba is present in all 594 genomes, with 94.1–100% nucleic acid identity

Summary

Introduction

The ongoing emergence of multidrug resistant strains of Neisseria gonorrhoeae is a major challenge to the management of the sexually transmitted infection gonorrhoea [1,2]. The World Health Organization [3], Centers for Disease Control [4], and Australian National Antimicrobial Resistance (AMR) Strategy [5] have prioritised N. gonorrhoeae as an urgent public health threat for which immediate action is needed. There are estimated to be more than 106 million cases of gonorrhoea worldwide each year [6] and infection rates are rising Infection with N. gonorrhoeae increases the risk of acquiring and transmitting HIV. Due to its high prevalence, the severe sequelae it can cause, and the increasing difficulty of treating multi-drug resistant strains of N. gonorrhoeae, there is an urgent need for the development of a vaccine to prevent infection

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