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

Vaccine potential of Adhesin Complex Protein (ACP) from Neisseria gonorrhoeae
Vaccine potential of Adhesin Complex Protein (ACP) from Neisseria gonorrhoeae
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.
University of Southampton
Almonacid Mendoza, Hannia Liliana
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Almonacid Mendoza, Hannia Liliana
5ef98c79-11f8-48c8-a9dc-fdcbec45c96b
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078
Clarke, Ian
ff6c9324-3547-4039-bb2c-10c0b3327a8b
McCormick, C.
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Almonacid Mendoza, Hannia Liliana (2017) Vaccine potential of Adhesin Complex Protein (ACP) from Neisseria gonorrhoeae. University of Southampton, Doctoral Thesis, 322pp.

Record type: Thesis (Doctoral)

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.

Text
Final thesis Hannia Almonacid Mendoza - Version of Record
Available under License University of Southampton Thesis Licence.
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Published date: December 2017

Identifiers

Local EPrints ID: 435480
URI: https://eprints.soton.ac.uk/id/eprint/435480
PURE UUID: d3ac11f6-5d0b-480e-816e-d9f156e50ae0
ORCID for Ian Clarke: ORCID iD orcid.org/0000-0002-4938-1620

Catalogue record

Date deposited: 07 Nov 2019 17:30
Last modified: 08 Nov 2019 01:39

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Contributors

Author: Hannia Liliana Almonacid Mendoza
Thesis advisor: Myron Christodoulides
Thesis advisor: Ian Clarke ORCID iD
Thesis advisor: C. McCormick

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