Vaccine potential of Adhesin Complex Protein (ACP) from Neisseria gonorrhoeae

Abstract

Sexual transmitted disease Gonorrhoea is caused by the organism Neisseria gonorrhoeae, infecting ~106 million cases annually. Currently, a lack of an effective vaccine against this pathogen and treatments using last generation of antibiotics are misleading due to emerging antibiotic-resistant superbugs. Recently has been described a small protein in a closed related bacteria, N. meningitidis (Nm), termed as an Adhesin Complex Protein (ACP). Nm-ACP is an outer-membrane protein which is a conserved protein in commensal and pathogenic bacteria. Besides Nm-ACP is capable of induce cross-protective bactericidal antibodies. A homologue gene, ng-acp (NGO1981) from Neisseria gonorrhoeae strain P9-17 is highly conserved among gonococcal isolates reported until the date. The ng-acp gene product was cloned into pRSET-A and pET-22b cloning vector systems and expressed as a recombinant protein in E. coli BL21pLysS to be used in immunization trials in murine model using a range of adjuvants and delivery formulations. Raised mice serum demonstrated a great reactivity against recombinant rNg-ACP by ELISA and displayed cross-strain reactivity in gonococcal outer-membrane (OMV) and lysate preparations from N. gonorrhoeae strains P9-17 and FA1090 by western-blot. Antisera r-Ng-ACP showed high bactericidal properties against homologous and heterologous wild type strains compared to the knockout strains. Furthermore, Ng-ACP plays a role of association on different epithelial cells showing a reduction ̴75-50% by comparison the wild-type and knockout. Three–dimensional structure of rNgACP the overall fold resemble of the lysozyme inhibitors from Salmonella typhimurium (PliC family) and recently described Neisseria meningitidis.Taken all together, suggest that Ng-ACP from N. gonorrhoeae is a potential candidate to develop an anti-gonococcal vaccine.

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Identifiers

ORCID for Myron Christodoulides: orcid.org/0000-0002-9663-4731

ORCID for Ian Clarke: orcid.org/0000-0002-4938-1620

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