promiscuous T cell epitope-based HIV vaccine providing redundant population coverage of the HLA class II elicits broad, polyfunctional T cell responses in nonhuman primate

Author(s):Show less -

Ribeiro, Susan Pereira ^{[1, 2, 3, 4]} ; De Moura Mattaraia, Vania Gomes ^[5] ; Almeida, Rafael Ribeiro ^{[1, 2, 4]} ; Ghiuro Valentine, Elizabeth Juliana ^[5] ; Sales, Natiely Silva ^[6] ; Ferreira, Luis Carlos S. ^[6] ; Sa-Rocha, Luiz Carlos ^[7] ; Jacintho, Lucas Caue ^{[1, 4]} ; Santana, Vinicius Canato ^{[1, 2, 4]} ; Sidney, John ^[8] ; Sette, Alessandro ^[8] ; Rosa, Daniela Santoro ^{[1, 9]} ; Kalil, Jorge ^{[1, 2, 4]} ; Cunha-Neto, Edecio ^{[1, 2, 4]}

Affiliation

^[1] Inst Invest Immunol Iii INCT, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Heart Inst, Lab Immunol, Sao Paulo - Brazil

^[3] Emory Univ, Atlanta, GA 30322 - USA

^[4] Univ Sao Paulo, Lab Clin Immunol & Allergy LIM60, Sch Med, Sao Paulo - Brazil

^[5] Butantan Inst, Sao Paulo, SP - Brazil

^[6] Univ Sao Paulo, Dept Microbiol, Inst Biomed Sci, Sao Paulo - Brazil

^[7] Univ Sao Paulo, Fac Vet Med & Zootechny, Sao Paulo - Brazil

^[8] La Jolla Inst Immunol LJI, La Jolla, CA - USA

^[9] Fed Univ Sao Paulo UNIFESP EPM, Dept Microbiol Immunol & Parasitol, Sao Paulo - Brazil

• Document type: Journal article
• Source: Vaccine; v. 40, n. 2, p. 239-246, JAN 21 2022.
• Web of Science Citations: 0

Abstract

Over the last few decades, several emerging or reemerging viral diseases with no readily available vaccines have ravaged the world. A platform to fastly generate vaccines inducing potent and durable neutralizing antibody and T cell responses is sorely needed. Bioinformatically identified epitope-based vaccines can focus on immunodominant T cell epitopes and induce more potent immune responses than a whole antigen vaccine and may be deployed more rapidly and less costly than whole-gene vaccines. Increasing evidence has shown the importance of the CD4+ T cell response in protection against HIV and other viral infections. The previously described DNA vaccine HIVBr18 encodes 18 conserved, promiscuous epitopes binding to multiple HLA-DR-binding HIV epitopes amply recognized by HIV-1-infected patients. HIVBr18 elicited broad, polyfunctional, and durable CD4(+) and CD8+ T cell responses in BALB/c and mice transgenic to HLA class II alleles, showing cross-species promiscuity. To fully delineate the promiscuity of the HLA class II vaccine epitopes, we assessed their binding to 34 human class II (HLA-DR, DQ, and -DP) molecules, and immunized nonhuman primates. Results ascertained redundant 100% coverage of the human population for multiple peptides. We then immunized Rhesus macaques with HIVBr18 under in vivo electroporation. The immunization induced strong, predominantly polyfunctional CD4+ T cell responses in all animals to 13 out of the 18 epitopes; T cells from each animal recognized 7-11 epitopes. Our results provide a preliminary proof of concept that immunization with a vaccine encoding epitopes with high and redundant coverage of the human population can elicit potent T cell responses to multiple epitopes, across species and MHC barriers. This approach may facilitate the rapid deployment of immunogens eliciting cellular immunity against emerging infectious diseases, such as COVID-19. (C) 2021 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 14/50890-5 - INCT of Investigation in Immunology
• Grantee: Jorge Elias Kalil Filho
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/50302-3 - Identification of predictive / prognostic genetic signature in Chagas cardiomyopathy: a systems biology approach
• Grantee: Edecio Cunha Neto
• Support Opportunities: Regular Research Grants