Broad and cross-clade CD4+ T-cell responses elicited by a DNA vaccine encoding highly conserved and promiscuous HIV-1 M-group consensus peptides.

T-cell based vaccine approaches have emerged to counteract HIV-1/AIDS. Broad, polyfunctional and cytotoxic CD4(+) T-cell responses have been associated with control of HIV-1 replication, which supports the inclusion of CD4(+) T-cell epitopes in vaccines. A successful HIV-1 vaccine should also be des...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Rafael Ribeiro Almeida, Daniela Santoro Rosa, Susan Pereira Ribeiro, Vinicius Canato Santana, Esper Georges Kallás, John Sidney, Alessandro Sette, Jorge Kalil, Edecio Cunha-Neto
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2012
Materias:
R
Q
Acceso en línea:https://doaj.org/article/fd5c5ee41c93441cbb27af5bf24da443
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:fd5c5ee41c93441cbb27af5bf24da443
record_format dspace
spelling oai:doaj.org-article:fd5c5ee41c93441cbb27af5bf24da4432021-11-18T07:05:10ZBroad and cross-clade CD4+ T-cell responses elicited by a DNA vaccine encoding highly conserved and promiscuous HIV-1 M-group consensus peptides.1932-620310.1371/journal.pone.0045267https://doaj.org/article/fd5c5ee41c93441cbb27af5bf24da4432012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23028895/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203T-cell based vaccine approaches have emerged to counteract HIV-1/AIDS. Broad, polyfunctional and cytotoxic CD4(+) T-cell responses have been associated with control of HIV-1 replication, which supports the inclusion of CD4(+) T-cell epitopes in vaccines. A successful HIV-1 vaccine should also be designed to overcome viral genetic diversity and be able to confer immunity in a high proportion of immunized individuals from a diverse HLA-bearing population. In this study, we rationally designed a multiepitopic DNA vaccine in order to elicit broad and cross-clade CD4(+) T-cell responses against highly conserved and promiscuous peptides from the HIV-1 M-group consensus sequence. We identified 27 conserved, multiple HLA-DR-binding peptides in the HIV-1 M-group consensus sequences of Gag, Pol, Nef, Vif, Vpr, Rev and Vpu using the TEPITOPE algorithm. The peptides bound in vitro to an average of 12 out of the 17 tested HLA-DR molecules and also to several molecules such as HLA-DP, -DQ and murine IA(b) and IA(d). Sixteen out of the 27 peptides were recognized by PBMC from patients infected with different HIV-1 variants and 72% of such patients recognized at least 1 peptide. Immunization with a DNA vaccine (HIVBr27) encoding the identified peptides elicited IFN-γ secretion against 11 out of the 27 peptides in BALB/c mice; CD4(+) and CD8(+) T-cell proliferation was observed against 8 and 6 peptides, respectively. HIVBr27 immunization elicited cross-clade T-cell responses against several HIV-1 peptide variants. Polyfunctional CD4(+) and CD8(+) T cells, able to simultaneously proliferate and produce IFN-γ and TNF-α, were also observed. This vaccine concept may cope with HIV-1 genetic diversity as well as provide increased population coverage, which are desirable features for an efficacious strategy against HIV-1/AIDS.Rafael Ribeiro AlmeidaDaniela Santoro RosaSusan Pereira RibeiroVinicius Canato SantanaEsper Georges KallásJohn SidneyAlessandro SetteJorge KalilEdecio Cunha-NetoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e45267 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Rafael Ribeiro Almeida
Daniela Santoro Rosa
Susan Pereira Ribeiro
Vinicius Canato Santana
Esper Georges Kallás
John Sidney
Alessandro Sette
Jorge Kalil
Edecio Cunha-Neto
Broad and cross-clade CD4+ T-cell responses elicited by a DNA vaccine encoding highly conserved and promiscuous HIV-1 M-group consensus peptides.
description T-cell based vaccine approaches have emerged to counteract HIV-1/AIDS. Broad, polyfunctional and cytotoxic CD4(+) T-cell responses have been associated with control of HIV-1 replication, which supports the inclusion of CD4(+) T-cell epitopes in vaccines. A successful HIV-1 vaccine should also be designed to overcome viral genetic diversity and be able to confer immunity in a high proportion of immunized individuals from a diverse HLA-bearing population. In this study, we rationally designed a multiepitopic DNA vaccine in order to elicit broad and cross-clade CD4(+) T-cell responses against highly conserved and promiscuous peptides from the HIV-1 M-group consensus sequence. We identified 27 conserved, multiple HLA-DR-binding peptides in the HIV-1 M-group consensus sequences of Gag, Pol, Nef, Vif, Vpr, Rev and Vpu using the TEPITOPE algorithm. The peptides bound in vitro to an average of 12 out of the 17 tested HLA-DR molecules and also to several molecules such as HLA-DP, -DQ and murine IA(b) and IA(d). Sixteen out of the 27 peptides were recognized by PBMC from patients infected with different HIV-1 variants and 72% of such patients recognized at least 1 peptide. Immunization with a DNA vaccine (HIVBr27) encoding the identified peptides elicited IFN-γ secretion against 11 out of the 27 peptides in BALB/c mice; CD4(+) and CD8(+) T-cell proliferation was observed against 8 and 6 peptides, respectively. HIVBr27 immunization elicited cross-clade T-cell responses against several HIV-1 peptide variants. Polyfunctional CD4(+) and CD8(+) T cells, able to simultaneously proliferate and produce IFN-γ and TNF-α, were also observed. This vaccine concept may cope with HIV-1 genetic diversity as well as provide increased population coverage, which are desirable features for an efficacious strategy against HIV-1/AIDS.
format article
author Rafael Ribeiro Almeida
Daniela Santoro Rosa
Susan Pereira Ribeiro
Vinicius Canato Santana
Esper Georges Kallás
John Sidney
Alessandro Sette
Jorge Kalil
Edecio Cunha-Neto
author_facet Rafael Ribeiro Almeida
Daniela Santoro Rosa
Susan Pereira Ribeiro
Vinicius Canato Santana
Esper Georges Kallás
John Sidney
Alessandro Sette
Jorge Kalil
Edecio Cunha-Neto
author_sort Rafael Ribeiro Almeida
title Broad and cross-clade CD4+ T-cell responses elicited by a DNA vaccine encoding highly conserved and promiscuous HIV-1 M-group consensus peptides.
title_short Broad and cross-clade CD4+ T-cell responses elicited by a DNA vaccine encoding highly conserved and promiscuous HIV-1 M-group consensus peptides.
title_full Broad and cross-clade CD4+ T-cell responses elicited by a DNA vaccine encoding highly conserved and promiscuous HIV-1 M-group consensus peptides.
title_fullStr Broad and cross-clade CD4+ T-cell responses elicited by a DNA vaccine encoding highly conserved and promiscuous HIV-1 M-group consensus peptides.
title_full_unstemmed Broad and cross-clade CD4+ T-cell responses elicited by a DNA vaccine encoding highly conserved and promiscuous HIV-1 M-group consensus peptides.
title_sort broad and cross-clade cd4+ t-cell responses elicited by a dna vaccine encoding highly conserved and promiscuous hiv-1 m-group consensus peptides.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/fd5c5ee41c93441cbb27af5bf24da443
work_keys_str_mv AT rafaelribeiroalmeida broadandcrosscladecd4tcellresponseselicitedbyadnavaccineencodinghighlyconservedandpromiscuoushiv1mgroupconsensuspeptides
AT danielasantororosa broadandcrosscladecd4tcellresponseselicitedbyadnavaccineencodinghighlyconservedandpromiscuoushiv1mgroupconsensuspeptides
AT susanpereiraribeiro broadandcrosscladecd4tcellresponseselicitedbyadnavaccineencodinghighlyconservedandpromiscuoushiv1mgroupconsensuspeptides
AT viniciuscanatosantana broadandcrosscladecd4tcellresponseselicitedbyadnavaccineencodinghighlyconservedandpromiscuoushiv1mgroupconsensuspeptides
AT espergeorgeskallas broadandcrosscladecd4tcellresponseselicitedbyadnavaccineencodinghighlyconservedandpromiscuoushiv1mgroupconsensuspeptides
AT johnsidney broadandcrosscladecd4tcellresponseselicitedbyadnavaccineencodinghighlyconservedandpromiscuoushiv1mgroupconsensuspeptides
AT alessandrosette broadandcrosscladecd4tcellresponseselicitedbyadnavaccineencodinghighlyconservedandpromiscuoushiv1mgroupconsensuspeptides
AT jorgekalil broadandcrosscladecd4tcellresponseselicitedbyadnavaccineencodinghighlyconservedandpromiscuoushiv1mgroupconsensuspeptides
AT edeciocunhaneto broadandcrosscladecd4tcellresponseselicitedbyadnavaccineencodinghighlyconservedandpromiscuoushiv1mgroupconsensuspeptides
_version_ 1718424017766973440