A DNA Vaccine Encoding Multiple HIV CD4 Epitopes Elicits Vigorous Polyfunctional, Long-Lived CD4(+) and CD8(+) T Cell Responses
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
dARK ID: | ark:/48912/001300000dfqq |
DOI: | 10.1371/journal.pone.0016921 |
Texto Completo: | http://dx.doi.org/10.1371/journal.pone.0016921 http://repositorio.unifesp.br/handle/11600/33463 |
Resumo: | T-cell based vaccines against HIV have the goal of limiting both transmission and disease progression by inducing broad and functionally relevant T cell responses. Moreover, polyfunctional and long-lived specific memory T cells have been associated to vaccine-induced protection. CD4(+) T cells are important for the generation and maintenance of functional CD8(+) cytotoxic T cells. We have recently developed a DNA vaccine encoding 18 conserved multiple HLA-DR-binding HIV-1 CD4 epitopes (HIVBr18), capable of eliciting broad CD4(+) T cell responses in multiple HLA class II transgenic mice. Here, we evaluated the breadth and functional profile of HIVBr18-induced immune responses in BALB/c mice. Immunized mice displayed high-magnitude, broad CD4(+)/CD8(+) T cell responses, and 8/18 vaccine-encoded peptides were recognized. in addition, HIVBr18 immunization was able to induce polyfunctional CD4(+) and CD8(+) T cells that proliferate and produce any two cytokines (IFN gamma/TNF alpha, IFN gamma/IL-2 or TNF alpha/IL-2) simultaneously in response to HIV-1 peptides. for CD4(+) T cells exclusively, we also detected cells that proliferate and produce all three tested cytokines simultaneously (IFN gamma/TNF alpha/IL-2). the vaccine also generated long-lived central and effector memory CD4(+) T cells, a desirable feature for T-cell based vaccines. By virtue of inducing broad, polyfunctional and long-lived T cell responses against conserved CD4(+) T cell epitopes, combined administration of this vaccine concept may provide sustained help for CD8(+) T cells and antibody responses-elicited by other HIV immunogens. |
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A DNA Vaccine Encoding Multiple HIV CD4 Epitopes Elicits Vigorous Polyfunctional, Long-Lived CD4(+) and CD8(+) T Cell ResponsesT-cell based vaccines against HIV have the goal of limiting both transmission and disease progression by inducing broad and functionally relevant T cell responses. Moreover, polyfunctional and long-lived specific memory T cells have been associated to vaccine-induced protection. CD4(+) T cells are important for the generation and maintenance of functional CD8(+) cytotoxic T cells. We have recently developed a DNA vaccine encoding 18 conserved multiple HLA-DR-binding HIV-1 CD4 epitopes (HIVBr18), capable of eliciting broad CD4(+) T cell responses in multiple HLA class II transgenic mice. Here, we evaluated the breadth and functional profile of HIVBr18-induced immune responses in BALB/c mice. Immunized mice displayed high-magnitude, broad CD4(+)/CD8(+) T cell responses, and 8/18 vaccine-encoded peptides were recognized. in addition, HIVBr18 immunization was able to induce polyfunctional CD4(+) and CD8(+) T cells that proliferate and produce any two cytokines (IFN gamma/TNF alpha, IFN gamma/IL-2 or TNF alpha/IL-2) simultaneously in response to HIV-1 peptides. for CD4(+) T cells exclusively, we also detected cells that proliferate and produce all three tested cytokines simultaneously (IFN gamma/TNF alpha/IL-2). the vaccine also generated long-lived central and effector memory CD4(+) T cells, a desirable feature for T-cell based vaccines. By virtue of inducing broad, polyfunctional and long-lived T cell responses against conserved CD4(+) T cell epitopes, combined administration of this vaccine concept may provide sustained help for CD8(+) T cells and antibody responses-elicited by other HIV immunogens.Univ São Paulo, Sch Med, Div Clin Immunol & Allergy, Dept Med,Lab Clin Immunol & Allergy LIM60, São Paulo, BrazilUniv São Paulo, Sch Med, Heart Inst InCor, São Paulo, BrazilInst Invest Immunol INCT, São Paulo, BrazilFed Univ São Paulo UNIFESP, Div Immunol, São Paulo, BrazilFed Univ São Paulo UNIFESP, Div Immunol, São Paulo, BrazilWeb of ScienceConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)International Centre of Genetic Engineering and Biotechnology (ICGEB)Brazilian Ministry of Health (Brazil)Public Library ScienceUniversidade de São Paulo (USP)Inst Invest Immunol INCTUniversidade Federal de São Paulo (UNIFESP)Rosa, Daniela Santoro [UNIFESP]Ribeiro, Susan PereiraAlmeida, Rafael RibeiroMairena, Eliane ContiPostol, EdilbertoKalil, JorgeCunha-Neto, Edecio2016-01-24T14:06:11Z2016-01-24T14:06:11Z2011-02-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion13application/pdfhttp://dx.doi.org/10.1371/journal.pone.0016921Plos One. San Francisco: Public Library Science, v. 6, n. 2, 13 p., 2011.10.1371/journal.pone.0016921WOS000287364500013.pdf1932-6203http://repositorio.unifesp.br/handle/11600/33463WOS:000287364500013ark:/48912/001300000dfqqengPlos Oneinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-08T01:29:38Zoai:repositorio.unifesp.br/:11600/33463Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-12-11T20:13:03.186603Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.none.fl_str_mv |
A DNA Vaccine Encoding Multiple HIV CD4 Epitopes Elicits Vigorous Polyfunctional, Long-Lived CD4(+) and CD8(+) T Cell Responses |
title |
A DNA Vaccine Encoding Multiple HIV CD4 Epitopes Elicits Vigorous Polyfunctional, Long-Lived CD4(+) and CD8(+) T Cell Responses |
spellingShingle |
A DNA Vaccine Encoding Multiple HIV CD4 Epitopes Elicits Vigorous Polyfunctional, Long-Lived CD4(+) and CD8(+) T Cell Responses A DNA Vaccine Encoding Multiple HIV CD4 Epitopes Elicits Vigorous Polyfunctional, Long-Lived CD4(+) and CD8(+) T Cell Responses Rosa, Daniela Santoro [UNIFESP] Rosa, Daniela Santoro [UNIFESP] |
title_short |
A DNA Vaccine Encoding Multiple HIV CD4 Epitopes Elicits Vigorous Polyfunctional, Long-Lived CD4(+) and CD8(+) T Cell Responses |
title_full |
A DNA Vaccine Encoding Multiple HIV CD4 Epitopes Elicits Vigorous Polyfunctional, Long-Lived CD4(+) and CD8(+) T Cell Responses |
title_fullStr |
A DNA Vaccine Encoding Multiple HIV CD4 Epitopes Elicits Vigorous Polyfunctional, Long-Lived CD4(+) and CD8(+) T Cell Responses A DNA Vaccine Encoding Multiple HIV CD4 Epitopes Elicits Vigorous Polyfunctional, Long-Lived CD4(+) and CD8(+) T Cell Responses |
title_full_unstemmed |
A DNA Vaccine Encoding Multiple HIV CD4 Epitopes Elicits Vigorous Polyfunctional, Long-Lived CD4(+) and CD8(+) T Cell Responses A DNA Vaccine Encoding Multiple HIV CD4 Epitopes Elicits Vigorous Polyfunctional, Long-Lived CD4(+) and CD8(+) T Cell Responses |
title_sort |
A DNA Vaccine Encoding Multiple HIV CD4 Epitopes Elicits Vigorous Polyfunctional, Long-Lived CD4(+) and CD8(+) T Cell Responses |
author |
Rosa, Daniela Santoro [UNIFESP] |
author_facet |
Rosa, Daniela Santoro [UNIFESP] Rosa, Daniela Santoro [UNIFESP] Ribeiro, Susan Pereira Almeida, Rafael Ribeiro Mairena, Eliane Conti Postol, Edilberto Kalil, Jorge Cunha-Neto, Edecio Ribeiro, Susan Pereira Almeida, Rafael Ribeiro Mairena, Eliane Conti Postol, Edilberto Kalil, Jorge Cunha-Neto, Edecio |
author_role |
author |
author2 |
Ribeiro, Susan Pereira Almeida, Rafael Ribeiro Mairena, Eliane Conti Postol, Edilberto Kalil, Jorge Cunha-Neto, Edecio |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Inst Invest Immunol INCT Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Rosa, Daniela Santoro [UNIFESP] Ribeiro, Susan Pereira Almeida, Rafael Ribeiro Mairena, Eliane Conti Postol, Edilberto Kalil, Jorge Cunha-Neto, Edecio |
description |
T-cell based vaccines against HIV have the goal of limiting both transmission and disease progression by inducing broad and functionally relevant T cell responses. Moreover, polyfunctional and long-lived specific memory T cells have been associated to vaccine-induced protection. CD4(+) T cells are important for the generation and maintenance of functional CD8(+) cytotoxic T cells. We have recently developed a DNA vaccine encoding 18 conserved multiple HLA-DR-binding HIV-1 CD4 epitopes (HIVBr18), capable of eliciting broad CD4(+) T cell responses in multiple HLA class II transgenic mice. Here, we evaluated the breadth and functional profile of HIVBr18-induced immune responses in BALB/c mice. Immunized mice displayed high-magnitude, broad CD4(+)/CD8(+) T cell responses, and 8/18 vaccine-encoded peptides were recognized. in addition, HIVBr18 immunization was able to induce polyfunctional CD4(+) and CD8(+) T cells that proliferate and produce any two cytokines (IFN gamma/TNF alpha, IFN gamma/IL-2 or TNF alpha/IL-2) simultaneously in response to HIV-1 peptides. for CD4(+) T cells exclusively, we also detected cells that proliferate and produce all three tested cytokines simultaneously (IFN gamma/TNF alpha/IL-2). the vaccine also generated long-lived central and effector memory CD4(+) T cells, a desirable feature for T-cell based vaccines. By virtue of inducing broad, polyfunctional and long-lived T cell responses against conserved CD4(+) T cell epitopes, combined administration of this vaccine concept may provide sustained help for CD8(+) T cells and antibody responses-elicited by other HIV immunogens. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011-02-11 2016-01-24T14:06:11Z 2016-01-24T14:06:11Z |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1371/journal.pone.0016921 Plos One. San Francisco: Public Library Science, v. 6, n. 2, 13 p., 2011. 10.1371/journal.pone.0016921 WOS000287364500013.pdf 1932-6203 http://repositorio.unifesp.br/handle/11600/33463 WOS:000287364500013 |
dc.identifier.dark.fl_str_mv |
ark:/48912/001300000dfqq |
url |
http://dx.doi.org/10.1371/journal.pone.0016921 http://repositorio.unifesp.br/handle/11600/33463 |
identifier_str_mv |
Plos One. San Francisco: Public Library Science, v. 6, n. 2, 13 p., 2011. 10.1371/journal.pone.0016921 WOS000287364500013.pdf 1932-6203 WOS:000287364500013 ark:/48912/001300000dfqq |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Plos One |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
13 application/pdf |
dc.publisher.none.fl_str_mv |
Public Library Science |
publisher.none.fl_str_mv |
Public Library Science |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
biblioteca.csp@unifesp.br |
_version_ |
1822183946648027136 |
dc.identifier.doi.none.fl_str_mv |
10.1371/journal.pone.0016921 |