Two Vaccines for <italic toggle="yes">Staphylococcus aureus</italic> Induce a B-Cell-Mediated Immune Response

ABSTRACT 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 efficac...

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Autores principales:	Christopher D. Dupont, Ingrid L. Scully, Ross M. Zimnisky, Brinda Monian, Christina P. Rossitto, Ellen B. O'Connell, Kathrin U. Jansen, Annaliesa S. Anderson, J. Christopher Love
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	immunization memory B cells microengraving Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ec62c241bbc54b0ca93bc9305e01660a
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spelling	oai:doaj.org-article:ec62c241bbc54b0ca93bc9305e01660a2021-11-15T15:25:50ZTwo Vaccines for <italic toggle="yes">Staphylococcus aureus</italic> Induce a B-Cell-Mediated Immune Response10.1128/mSphere.00217-182379-5042https://doaj.org/article/ec62c241bbc54b0ca93bc9305e01660a2018-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00217-18https://doaj.org/toc/2379-5042ABSTRACT 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 TH17 and/or TH1 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 TH17 or TH1 response evident. However, our data are consistent with a vaccine-induced recruitment of T follicular helper (TFH) 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.Christopher D. DupontIngrid L. ScullyRoss M. ZimniskyBrinda MonianChristina P. RossittoEllen B. O'ConnellKathrin U. JansenAnnaliesa S. AndersonJ. Christopher LoveAmerican Society for Microbiologyarticleimmunizationmemory B cellsmicroengravingMicrobiologyQR1-502ENmSphere, Vol 3, Iss 4 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	immunization memory B cells microengraving Microbiology QR1-502
spellingShingle	immunization memory B cells microengraving Microbiology QR1-502 Christopher D. Dupont Ingrid L. Scully Ross M. Zimnisky Brinda Monian Christina P. Rossitto Ellen B. O'Connell Kathrin U. Jansen Annaliesa S. Anderson J. Christopher Love Two Vaccines for <italic toggle="yes">Staphylococcus aureus</italic> Induce a B-Cell-Mediated Immune Response
description	ABSTRACT 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 TH17 and/or TH1 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 TH17 or TH1 response evident. However, our data are consistent with a vaccine-induced recruitment of T follicular helper (TFH) 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.
format	article
author	Christopher D. Dupont Ingrid L. Scully Ross M. Zimnisky Brinda Monian Christina P. Rossitto Ellen B. O'Connell Kathrin U. Jansen Annaliesa S. Anderson J. Christopher Love
author_facet	Christopher D. Dupont Ingrid L. Scully Ross M. Zimnisky Brinda Monian Christina P. Rossitto Ellen B. O'Connell Kathrin U. Jansen Annaliesa S. Anderson J. Christopher Love
author_sort	Christopher D. Dupont
title	Two Vaccines for <italic toggle="yes">Staphylococcus aureus</italic> Induce a B-Cell-Mediated Immune Response
title_short	Two Vaccines for <italic toggle="yes">Staphylococcus aureus</italic> Induce a B-Cell-Mediated Immune Response
title_full	Two Vaccines for <italic toggle="yes">Staphylococcus aureus</italic> Induce a B-Cell-Mediated Immune Response
title_fullStr	Two Vaccines for <italic toggle="yes">Staphylococcus aureus</italic> Induce a B-Cell-Mediated Immune Response
title_full_unstemmed	Two Vaccines for <italic toggle="yes">Staphylococcus aureus</italic> Induce a B-Cell-Mediated Immune Response
title_sort	two vaccines for <italic toggle="yes">staphylococcus aureus</italic> induce a b-cell-mediated immune response
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/ec62c241bbc54b0ca93bc9305e01660a
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Two Vaccines for <italic toggle="yes">Staphylococcus aureus</italic> Induce a B-Cell-Mediated Immune Response

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