A DNA Vaccine Encoding Multiple HIV CD4 Epitopes Elicits Vigorous Polyfunctional, Long-Lived CD4(+) and CD8(+) T Cell Responses

Detalhes bibliográficos
Autor(a) principal: Rosa, Daniela Santoro [UNIFESP]
Data de Publicação: 2011
Outros Autores: Ribeiro, Susan Pereira, Almeida, Rafael Ribeiro, Mairena, Eliane Conti, Postol, Edilberto, Kalil, Jorge, Cunha-Neto, Edecio
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.
id UFSP_bd5dab9c597bea05bb360368c0fb3700
oai_identifier_str oai:repositorio.unifesp.br/:11600/33463
network_acronym_str UFSP
network_name_str Repositório Institucional da UNIFESP
repository_id_str 3465
spelling 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