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Two Vaccines for Staphylococcus aureus Induce a B-Cell-Mediated Immune Response

Staphylococcus aureus causes severe disease in humans for which no licensed vaccine exists. A novel S. aureus vaccine (SA4Ag) is in development, targeting the capsular polysaccharides (CPs) and two virulence-associated surface proteins. Vaccine-elicited antibody responses to CPs are efficacious agai...

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Autores principales: Dupont, Christopher D., Scully, Ingrid L., Zimnisky, Ross M., Monian, Brinda, Rossitto, Christina P., O'Connell, Ellen B., Jansen, Kathrin U., Anderson, Annaliesa S., Love, J. Christopher
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106056/
https://www.ncbi.nlm.nih.gov/pubmed/30135219
http://dx.doi.org/10.1128/mSphere.00217-18
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author Dupont, Christopher D.
Scully, Ingrid L.
Zimnisky, Ross M.
Monian, Brinda
Rossitto, Christina P.
O'Connell, Ellen B.
Jansen, Kathrin U.
Anderson, Annaliesa S.
Love, J. Christopher
author_facet Dupont, Christopher D.
Scully, Ingrid L.
Zimnisky, Ross M.
Monian, Brinda
Rossitto, Christina P.
O'Connell, Ellen B.
Jansen, Kathrin U.
Anderson, Annaliesa S.
Love, J. Christopher
author_sort Dupont, Christopher D.
collection PubMed
description Staphylococcus aureus causes severe disease in humans for which no licensed vaccine exists. A novel S. aureus vaccine (SA4Ag) is in development, targeting the capsular polysaccharides (CPs) and two virulence-associated surface proteins. Vaccine-elicited antibody responses to CPs are efficacious against serious infection by other encapsulated bacteria. Studies of natural S. aureus infection have also shown a role for T(H)17 and/or T(H)1 responses in protection. Single-antigen vaccines, including CPs, have not been effective against S. aureus; a multiantigen vaccine approach is likely required. However, the impact of addition of protein antigens on the immune response to CPs has not been studied. Here, the immune response induced by a bivalent CP conjugate vaccine (to model the established mechanism of action of vaccine-induced protection against Gram-positive pathogens) was compared to the response induced by SA4Ag, which contains both CP conjugates and protein antigens, in cynomolgus macaques. Microengraving, flow cytometry, opsonophagocytic assays, and Luminex technology were used to analyze the B-cell, T-cell, functional antibody, and innate immune responses. Both the bivalent CP vaccine and SA4Ag induced cytokine production from naive cells and antigen-specific memory B-cell and functional antibody responses. Increases in levels of circulating, activated T cells were not apparent following vaccination, nor was a T(H)17 or T(H)1 response evident. However, our data are consistent with a vaccine-induced recruitment of T follicular helper (T(F)H) cells to lymph nodes. Collectively, these data suggest that the response to SA4Ag is primarily mediated by B cells and antibodies that abrogate important S. aureus virulence mechanisms. IMPORTANCE Staphylococcus aureus causes severe disease in humans for which no licensed vaccine exists. A novel vaccine is in development that targets multiple elements of the bacteria since single-component vaccines have not shown efficacy to date. How these multiple components alter the immune response raised by the vaccine is not well studied. We found that the addition of two protein components did not alter substantially the antibody responses raised with respect to function or mobilization of B cells. There was also not a substantial change in the activity of T cells, another part of the adaptive response. This study showed that protection by this vaccine may be mediated primarily by antibody protection.
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spelling pubmed-61060562018-08-31 Two Vaccines for Staphylococcus aureus Induce a B-Cell-Mediated Immune Response Dupont, Christopher D. Scully, Ingrid L. Zimnisky, Ross M. Monian, Brinda Rossitto, Christina P. O'Connell, Ellen B. Jansen, Kathrin U. Anderson, Annaliesa S. Love, J. Christopher mSphere Research Article Staphylococcus aureus causes severe disease in humans for which no licensed vaccine exists. A novel S. aureus vaccine (SA4Ag) is in development, targeting the capsular polysaccharides (CPs) and two virulence-associated surface proteins. Vaccine-elicited antibody responses to CPs are efficacious against serious infection by other encapsulated bacteria. Studies of natural S. aureus infection have also shown a role for T(H)17 and/or T(H)1 responses in protection. Single-antigen vaccines, including CPs, have not been effective against S. aureus; a multiantigen vaccine approach is likely required. However, the impact of addition of protein antigens on the immune response to CPs has not been studied. Here, the immune response induced by a bivalent CP conjugate vaccine (to model the established mechanism of action of vaccine-induced protection against Gram-positive pathogens) was compared to the response induced by SA4Ag, which contains both CP conjugates and protein antigens, in cynomolgus macaques. Microengraving, flow cytometry, opsonophagocytic assays, and Luminex technology were used to analyze the B-cell, T-cell, functional antibody, and innate immune responses. Both the bivalent CP vaccine and SA4Ag induced cytokine production from naive cells and antigen-specific memory B-cell and functional antibody responses. Increases in levels of circulating, activated T cells were not apparent following vaccination, nor was a T(H)17 or T(H)1 response evident. However, our data are consistent with a vaccine-induced recruitment of T follicular helper (T(F)H) cells to lymph nodes. Collectively, these data suggest that the response to SA4Ag is primarily mediated by B cells and antibodies that abrogate important S. aureus virulence mechanisms. IMPORTANCE Staphylococcus aureus causes severe disease in humans for which no licensed vaccine exists. A novel vaccine is in development that targets multiple elements of the bacteria since single-component vaccines have not shown efficacy to date. How these multiple components alter the immune response raised by the vaccine is not well studied. We found that the addition of two protein components did not alter substantially the antibody responses raised with respect to function or mobilization of B cells. There was also not a substantial change in the activity of T cells, another part of the adaptive response. This study showed that protection by this vaccine may be mediated primarily by antibody protection. American Society for Microbiology 2018-08-22 /pmc/articles/PMC6106056/ /pubmed/30135219 http://dx.doi.org/10.1128/mSphere.00217-18 Text en Copyright © 2018 Dupont et al. 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
Dupont, Christopher D.
Scully, Ingrid L.
Zimnisky, Ross M.
Monian, Brinda
Rossitto, Christina P.
O'Connell, Ellen B.
Jansen, Kathrin U.
Anderson, Annaliesa S.
Love, J. Christopher
Two Vaccines for Staphylococcus aureus Induce a B-Cell-Mediated Immune Response
title Two Vaccines for Staphylococcus aureus Induce a B-Cell-Mediated Immune Response
title_full Two Vaccines for Staphylococcus aureus Induce a B-Cell-Mediated Immune Response
title_fullStr Two Vaccines for Staphylococcus aureus Induce a B-Cell-Mediated Immune Response
title_full_unstemmed Two Vaccines for Staphylococcus aureus Induce a B-Cell-Mediated Immune Response
title_short Two Vaccines for Staphylococcus aureus Induce a B-Cell-Mediated Immune Response
title_sort two vaccines for staphylococcus aureus induce a b-cell-mediated immune response
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106056/
https://www.ncbi.nlm.nih.gov/pubmed/30135219
http://dx.doi.org/10.1128/mSphere.00217-18
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