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Immunogenic recombinant Burkholderia pseudomallei MprA serine protease elicits protective immunity in mice

Burkholderia pseudomallei is resistant to a diverse group of antimicrobials including third generation cephalosporins whilst quinolones and aminoglycosides have no reliable effect. As therapeutic options are limited, development of more effective forms of immunotherapy is vital to avoid a fatal outc...

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Autores principales: Chin, Chui-Yoke, Tan, Swee-Chen, Nathan, Sheila
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3417646/
https://www.ncbi.nlm.nih.gov/pubmed/22919676
http://dx.doi.org/10.3389/fcimb.2012.00085
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author Chin, Chui-Yoke
Tan, Swee-Chen
Nathan, Sheila
author_facet Chin, Chui-Yoke
Tan, Swee-Chen
Nathan, Sheila
author_sort Chin, Chui-Yoke
collection PubMed
description Burkholderia pseudomallei is resistant to a diverse group of antimicrobials including third generation cephalosporins whilst quinolones and aminoglycosides have no reliable effect. As therapeutic options are limited, development of more effective forms of immunotherapy is vital to avoid a fatal outcome. In an earlier study, we reported on the B. pseudomallei serine MprA protease, which is relatively stable over a wide pH and temperature range and digests physiological proteins. The present study was carried out to evaluate the immunogenicity and protective efficacy of the MprA as a potential vaccine candidate. In BALB/c mice immunized with recombinant MprA protease (smBpF4), a significantly high IgG titer was detectable. Isotyping studies revealed that the smBpF4-specific antibodies produced were predominantly IgG(1), proposing that immunization with smBpF4 triggered a Th2 immune response. Mice were immunized with smBpF4 and subsequently challenged with B. pseudomallei via the intraperitoneal route. Whilst control mice succumbed to the infection by day 9, smBpF4-immunized mice were protected against the lethal challenge and survived beyond 25 days post-infection. In conclusion, MprA is immunogenic in melioidosis patients whilst also eliciting a strong immune response upon bacterial challenge in mice and presents itself as a potential vaccine candidate for the treatment of melioidosis.
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spelling pubmed-34176462012-08-23 Immunogenic recombinant Burkholderia pseudomallei MprA serine protease elicits protective immunity in mice Chin, Chui-Yoke Tan, Swee-Chen Nathan, Sheila Front Cell Infect Microbiol Microbiology Burkholderia pseudomallei is resistant to a diverse group of antimicrobials including third generation cephalosporins whilst quinolones and aminoglycosides have no reliable effect. As therapeutic options are limited, development of more effective forms of immunotherapy is vital to avoid a fatal outcome. In an earlier study, we reported on the B. pseudomallei serine MprA protease, which is relatively stable over a wide pH and temperature range and digests physiological proteins. The present study was carried out to evaluate the immunogenicity and protective efficacy of the MprA as a potential vaccine candidate. In BALB/c mice immunized with recombinant MprA protease (smBpF4), a significantly high IgG titer was detectable. Isotyping studies revealed that the smBpF4-specific antibodies produced were predominantly IgG(1), proposing that immunization with smBpF4 triggered a Th2 immune response. Mice were immunized with smBpF4 and subsequently challenged with B. pseudomallei via the intraperitoneal route. Whilst control mice succumbed to the infection by day 9, smBpF4-immunized mice were protected against the lethal challenge and survived beyond 25 days post-infection. In conclusion, MprA is immunogenic in melioidosis patients whilst also eliciting a strong immune response upon bacterial challenge in mice and presents itself as a potential vaccine candidate for the treatment of melioidosis. Frontiers Media S.A. 2012-06-15 /pmc/articles/PMC3417646/ /pubmed/22919676 http://dx.doi.org/10.3389/fcimb.2012.00085 Text en Copyright © 2012 Chin, Tan and Nathan. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
spellingShingle Microbiology
Chin, Chui-Yoke
Tan, Swee-Chen
Nathan, Sheila
Immunogenic recombinant Burkholderia pseudomallei MprA serine protease elicits protective immunity in mice
title Immunogenic recombinant Burkholderia pseudomallei MprA serine protease elicits protective immunity in mice
title_full Immunogenic recombinant Burkholderia pseudomallei MprA serine protease elicits protective immunity in mice
title_fullStr Immunogenic recombinant Burkholderia pseudomallei MprA serine protease elicits protective immunity in mice
title_full_unstemmed Immunogenic recombinant Burkholderia pseudomallei MprA serine protease elicits protective immunity in mice
title_short Immunogenic recombinant Burkholderia pseudomallei MprA serine protease elicits protective immunity in mice
title_sort immunogenic recombinant burkholderia pseudomallei mpra serine protease elicits protective immunity in mice
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3417646/
https://www.ncbi.nlm.nih.gov/pubmed/22919676
http://dx.doi.org/10.3389/fcimb.2012.00085
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AT nathansheila immunogenicrecombinantburkholderiapseudomalleimpraserineproteaseelicitsprotectiveimmunityinmice