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Staphylococcal Enterotoxin B and C Mutants and Vaccine Toxoids

Three mutants individually of both staphylococcal enterotoxins B and C were prepared by site-specific mutagenesis of enterotoxin amino acids that contact host T lymphocyte immune cell receptor sites (N23A, Q210A, and N23A/Q210A); these amino acids are shared between the two enterotoxins, and mutatio...

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Autor principal: Schlievert, Patrick M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10101070/
https://www.ncbi.nlm.nih.gov/pubmed/36815779
http://dx.doi.org/10.1128/spectrum.04446-22
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author Schlievert, Patrick M.
author_facet Schlievert, Patrick M.
author_sort Schlievert, Patrick M.
collection PubMed
description Three mutants individually of both staphylococcal enterotoxins B and C were prepared by site-specific mutagenesis of enterotoxin amino acids that contact host T lymphocyte immune cell receptor sites (N23A, Q210A, and N23A/Q210A); these amino acids are shared between the two enterotoxins, and mutations reduce the interaction with the variable part of the β-chain of the T lymphocyte receptor. The mutant proteins, as expressed in Staphylococcus aureus RN4220, lacked biological toxicity as measured by the loss of (i) stimulation of rabbit splenocyte proliferation, (ii) pyrogenicity, and (iii) the ability to enhance the lethality of endotoxin shock, compared to wild-type enterotoxins. In addition, the mutants were able to vaccinate rabbits against pyrogenicity, the enhancement of endotoxin shock, and lethality in a pneumonia model when animals were challenged with methicillin-resistant S. aureus. Three vaccine injections (one primary and two boosters) protected rabbits for at least 3.5 months postvaccination when challenged with wild-type enterotoxins (last time point tested). These mutant proteins have the potential to function as toxoid vaccines against these two causes of nonmenstrual toxic shock syndrome (TSS). IMPORTANCE Toxic shock syndrome toxin 1 (TSST-1) and staphylococcal enterotoxins B and C cause the majority of cases of staphylococcal toxic shock syndrome. Previously, vaccine toxoids of TSST-1 have been prepared. In this study, vaccine toxoids of enterotoxins B and C were prepared. The toxoids lost biological toxicity but were able to vaccinate rabbits against lethal TSS.
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spelling pubmed-101010702023-04-14 Staphylococcal Enterotoxin B and C Mutants and Vaccine Toxoids Schlievert, Patrick M. Microbiol Spectr Research Article Three mutants individually of both staphylococcal enterotoxins B and C were prepared by site-specific mutagenesis of enterotoxin amino acids that contact host T lymphocyte immune cell receptor sites (N23A, Q210A, and N23A/Q210A); these amino acids are shared between the two enterotoxins, and mutations reduce the interaction with the variable part of the β-chain of the T lymphocyte receptor. The mutant proteins, as expressed in Staphylococcus aureus RN4220, lacked biological toxicity as measured by the loss of (i) stimulation of rabbit splenocyte proliferation, (ii) pyrogenicity, and (iii) the ability to enhance the lethality of endotoxin shock, compared to wild-type enterotoxins. In addition, the mutants were able to vaccinate rabbits against pyrogenicity, the enhancement of endotoxin shock, and lethality in a pneumonia model when animals were challenged with methicillin-resistant S. aureus. Three vaccine injections (one primary and two boosters) protected rabbits for at least 3.5 months postvaccination when challenged with wild-type enterotoxins (last time point tested). These mutant proteins have the potential to function as toxoid vaccines against these two causes of nonmenstrual toxic shock syndrome (TSS). IMPORTANCE Toxic shock syndrome toxin 1 (TSST-1) and staphylococcal enterotoxins B and C cause the majority of cases of staphylococcal toxic shock syndrome. Previously, vaccine toxoids of TSST-1 have been prepared. In this study, vaccine toxoids of enterotoxins B and C were prepared. The toxoids lost biological toxicity but were able to vaccinate rabbits against lethal TSS. American Society for Microbiology 2023-02-23 /pmc/articles/PMC10101070/ /pubmed/36815779 http://dx.doi.org/10.1128/spectrum.04446-22 Text en Copyright © 2023 Schlievert. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Schlievert, Patrick M.
Staphylococcal Enterotoxin B and C Mutants and Vaccine Toxoids
title Staphylococcal Enterotoxin B and C Mutants and Vaccine Toxoids
title_full Staphylococcal Enterotoxin B and C Mutants and Vaccine Toxoids
title_fullStr Staphylococcal Enterotoxin B and C Mutants and Vaccine Toxoids
title_full_unstemmed Staphylococcal Enterotoxin B and C Mutants and Vaccine Toxoids
title_short Staphylococcal Enterotoxin B and C Mutants and Vaccine Toxoids
title_sort staphylococcal enterotoxin b and c mutants and vaccine toxoids
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10101070/
https://www.ncbi.nlm.nih.gov/pubmed/36815779
http://dx.doi.org/10.1128/spectrum.04446-22
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