Antigen-specific antibody and polyfunctional T cells generated by respiratory immunization with protective Burkholderia ΔtonB Δhcp1 live attenuated vaccines

Abstract Melioidosis, caused by Burkholderia pseudomallei (Bpm), lacks a vaccine. We identify the immune correlates of protection induced by B. mallei ΔtonB Δhcp1 (CLH001) and Bpm ΔtonB Δhcp1 (PBK001) vaccines against inhalational melioidosis. Mucosal immunization with either vaccine generates Bpm-s...

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Autores principales:	Nittaya Khakhum, Preeti Bharaj, David H. Walker, Alfredo G. Torres, Janice J. Endsley
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/1ed07a95843f4f11b748cd921ed20a08
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spelling	oai:doaj.org-article:1ed07a95843f4f11b748cd921ed20a082021-12-02T15:54:45ZAntigen-specific antibody and polyfunctional T cells generated by respiratory immunization with protective Burkholderia ΔtonB Δhcp1 live attenuated vaccines10.1038/s41541-021-00333-42059-0105https://doaj.org/article/1ed07a95843f4f11b748cd921ed20a082021-05-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00333-4https://doaj.org/toc/2059-0105Abstract Melioidosis, caused by Burkholderia pseudomallei (Bpm), lacks a vaccine. We identify the immune correlates of protection induced by B. mallei ΔtonB Δhcp1 (CLH001) and Bpm ΔtonB Δhcp1 (PBK001) vaccines against inhalational melioidosis. Mucosal immunization with either vaccine generates Bpm-specific IgM and IgG (IgG2 b/c > IgG1 > IgG3) antibodies in sera and lungs, and lung IgA antibodies. Sera confers complement-independent bactericidal activity and macrophages opsonophagocytic uptake but is insufficient in passive transfer experiments to provide significant protection. Both vaccines elicit memory Th1 and Th17 CD4+ T-cell responses in lung and spleen after Bpm antigen-specific recall. The PBK001 vaccine is superior in generating respiratory IgA post-boost, anamnestic IgG at challenge, T-cell recall to specific antigen, and development of diverse polyfunctional memory T-cell pools. Analysis of lung histology suggests that potent polyfunctional T-cell memory and/or IL-17 signatures generated with PBK001 vaccination may be associated with moderate lung inflammation post vaccination.Nittaya KhakhumPreeti BharajDavid H. WalkerAlfredo G. TorresJanice J. EndsleyNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Nittaya Khakhum Preeti Bharaj David H. Walker Alfredo G. Torres Janice J. Endsley Antigen-specific antibody and polyfunctional T cells generated by respiratory immunization with protective Burkholderia ΔtonB Δhcp1 live attenuated vaccines
description	Abstract Melioidosis, caused by Burkholderia pseudomallei (Bpm), lacks a vaccine. We identify the immune correlates of protection induced by B. mallei ΔtonB Δhcp1 (CLH001) and Bpm ΔtonB Δhcp1 (PBK001) vaccines against inhalational melioidosis. Mucosal immunization with either vaccine generates Bpm-specific IgM and IgG (IgG2 b/c > IgG1 > IgG3) antibodies in sera and lungs, and lung IgA antibodies. Sera confers complement-independent bactericidal activity and macrophages opsonophagocytic uptake but is insufficient in passive transfer experiments to provide significant protection. Both vaccines elicit memory Th1 and Th17 CD4+ T-cell responses in lung and spleen after Bpm antigen-specific recall. The PBK001 vaccine is superior in generating respiratory IgA post-boost, anamnestic IgG at challenge, T-cell recall to specific antigen, and development of diverse polyfunctional memory T-cell pools. Analysis of lung histology suggests that potent polyfunctional T-cell memory and/or IL-17 signatures generated with PBK001 vaccination may be associated with moderate lung inflammation post vaccination.
format	article
author	Nittaya Khakhum Preeti Bharaj David H. Walker Alfredo G. Torres Janice J. Endsley
author_facet	Nittaya Khakhum Preeti Bharaj David H. Walker Alfredo G. Torres Janice J. Endsley
author_sort	Nittaya Khakhum
title	Antigen-specific antibody and polyfunctional T cells generated by respiratory immunization with protective Burkholderia ΔtonB Δhcp1 live attenuated vaccines
title_short	Antigen-specific antibody and polyfunctional T cells generated by respiratory immunization with protective Burkholderia ΔtonB Δhcp1 live attenuated vaccines
title_full	Antigen-specific antibody and polyfunctional T cells generated by respiratory immunization with protective Burkholderia ΔtonB Δhcp1 live attenuated vaccines
title_fullStr	Antigen-specific antibody and polyfunctional T cells generated by respiratory immunization with protective Burkholderia ΔtonB Δhcp1 live attenuated vaccines
title_full_unstemmed	Antigen-specific antibody and polyfunctional T cells generated by respiratory immunization with protective Burkholderia ΔtonB Δhcp1 live attenuated vaccines
title_sort	antigen-specific antibody and polyfunctional t cells generated by respiratory immunization with protective burkholderia δtonb δhcp1 live attenuated vaccines
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1ed07a95843f4f11b748cd921ed20a08
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Antigen-specific antibody and polyfunctional T cells generated by respiratory immunization with protective Burkholderia ΔtonB Δhcp1 live attenuated vaccines

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