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

Author(s)

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]}

Affiliation

^[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

• Document type: Journal article
• Source: PLoS One; v. 7, n. 9 SEP 18 2012.
• Web of Science Citations: 19

Abstract

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)

• FAPESP's process: 08/57881-0 - Institute for Investigation in Immunology
• Grantee: Jorge Elias Kalil Filho
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 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
• Grantee: Sabri Saeed Mohammed Ahmed Al-Sanabani
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 04/15856-9 - Prospective analysis of the virological and immunological characteristics in individuals with recent HIV-1 infection in the cities of São Paulo and Santos
• Grantee: Ricardo Sobhie Diaz
• Support type: Research Projects - Thematic Grants