Broad and Cross-Clade CD4(+) T-Cell Responses Elicited by a DNA Vaccine Encoding Highly Conserved and Promiscuous HIV-1 M-Group Consensus Peptides

Autor(es)

Almeida, Rafael Ribeiro ^[1] ; Rosa, Daniela Santoro ^{[2, 1, 3]} ; Ribeiro, Susan Pereira ^{[2, 1]} ; Santana, Vinicius Canato ^[1] ; Kallas, Esper Georges ^[1] ; Sidney, John ^[4] ; Sette, Alessandro ; Kalil, Jorge ^{[2, 1, 5]} ; Cunha-Neto, Edecio ^{[2, 1, 5]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Lab Clin Immunol & Allergy LIM60, Div Clin Immunol & Allergy, Dept Med, Sao Paulo - Brazil

^[2] INCT, Inst Invest Immunol, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, UNIFESP, Div Immunol, Sao Paulo - Brazil

^[4] La Jolla Inst Allergy & Immunol, Ctr Infect Dis Allergy & Asthma Res, La Jolla, CA - USA

^[5] Univ Sao Paulo, InCor, Sch Med, Inst Heart, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 7, n. 9 SEP 18 2012.
• Citações Web of Science: 19

Resumo

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-gamma 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-gamma and TNF-alpha, 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. (AU)

• Processo FAPESP: 08/57881-0 - Instituto de Investigação em Imunologia
• Beneficiário: Jorge Elias Kalil Filho
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 04/15856-9 - Análise prospectiva das características virológicas e imunológicas em indivíduos com infecção recente pelo HIV-1 das cidades de São Paulo e Santos, SP
• Beneficiário: Ricardo Sobhie Diaz
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 06/50096-0 - Characterization of Human Immunodeficiency Virus type 1 (HIV-1) in a cohort of recently infected persons from the State of São Paulo by full genome sequencing
• Beneficiário: Sabri Saeed Mohamed Ahmed Al-Sanabani
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado