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dc.contributor.authorJen, Freda E-C
dc.contributor.authorSemchenko, Evgeny A
dc.contributor.authorDay, Christopher J
dc.contributor.authorSeib, Kate L
dc.contributor.authorJennings, Michael P
dc.date.accessioned2019-09-09T00:03:54Z
dc.date.available2019-09-09T00:03:54Z
dc.date.issued2019
dc.identifier.issn1664-3224
dc.identifier.doi10.3389/fimmu.2019.00137
dc.identifier.urihttp://hdl.handle.net/10072/387028
dc.description.abstractControl of the sexually transmitted infection gonorrhea is a major public health challenge, due to the recent emergence of multidrug resistant strains of Neisseria gonorrhoeae, and there is an urgent need for novel therapies or a vaccine to prevent gonococcal disease. In this study, we evaluated the methionine sulfoxide reductase (MsrA/B) of N. gonorrhoeae as a potential vaccine candidate, in terms of its expression, sequence conservation, localization, immunogenicity, and the functional activity of antibodies raised to it. Gonococcal MsrA/B has previously been shown to reduce methionine sulfoxide [Met(O)] to methionine (Met) in oxidized proteins and protect against oxidative stress. Here we have shown that the gene encoding MsrA/B is present, highly conserved, and expressed in all N. gonorrhoeae strains investigated, and we determined that MsrA/B is surface is exposed on N. gonorrhoeae. Recombinant MsrA/B is immunogenic, and mice immunized with MsrA/B and either aluminum hydroxide gel adjuvant or Freund's adjuvant generated a humoral immune response, with predominantly IgG1 antibodies. Higher titers of IgG2a, IgG2b, and IgG3 were detected in mice immunized with MsrA/B-Freund's adjuvant compared to MsrA/B-aluminum hydroxide adjuvant, while IgM titers were similar for both adjuvants. Antibodies generated by MsrA/B-Freund's in mice mediated bacterial killing via both serum bactericidal activity and opsonophagocytic activity. Anti-MsrA/B was also able to functionally block the activity of MsrA/B by inhibiting binding to its substrate, Met(O). We propose that recombinant MsrA/B is a promising vaccine antigen for N. gonorrhoeae.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherFrontiers Media
dc.relation.ispartofissueFebruary
dc.relation.ispartofjournalFrontiers in immunology
dc.relation.ispartofvolume10
dc.relation.urihttp://purl.org/au-research/grants/NHMRC/APP1045235
dc.relation.grantIDAPP1045235
dc.relation.fundersNHMRC
dc.subject.fieldofresearchImmunology
dc.subject.fieldofresearchMedical microbiology
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchGenetics
dc.subject.fieldofresearchcode3204
dc.subject.fieldofresearchcode3207
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode3105
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsmethionine sulfoxide reductase
dc.subject.keywordsbactericidal activity
dc.titleThe Neisseria gonorrhoeae Methionine Sulfoxide Reductase (MsrA/B) Is a Surface Exposed, Immunogenic, Vaccine Candidate
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationJen, FE-C; Semchenko, EA; Day, CJ; Seib, KL; Jennings, MP, The Neisseria gonorrhoeae Methionine Sulfoxide Reductase (MsrA/B) Is a Surface Exposed, Immunogenic, Vaccine Candidate, Frontiers in immunology, 2019, 10 (February)
dcterms.dateAccepted2019-01-16
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.date.updated2019-09-09T00:00:08Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2019 Jen, Semchenko, Day, Seib and Jennings. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
gro.hasfulltextFull Text
gro.griffith.authorJennings, Michael P.
gro.griffith.authorJen, Freda E.
gro.griffith.authorSemchenko, Evgeny
gro.griffith.authorSeib, Kate
gro.griffith.authorDay, Christopher J.


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