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

• Published in: Vaccine 2022-01, Vol.40 (2), p.239-246
• Main Authors: Ribeiro, Susan Pereira, De Moura Mattaraia, Vania Gomes, Almeida, Rafael Ribeiro, Valentine, Elizabeth Juliana Ghiuro, Sales, Natiely Silva, Ferreira, Luís Carlos S., Sa-Rocha, Luiz Carlos, Jacintho, Lucas Cauê, Santana, Vinicius Canato, Sidney, John, Sette, Alessandro, Rosa, Daniela Santoro, Kalil, Jorge, Cunha-Neto, Edecio
• Format: Article
• Language: English
• Subjects: AIDS Vaccines - immunology; Animals; Antibodies; Antigens; Binding; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell-mediated immunity; COVID-19; DNA vaccine; DNA vaccines; Electroporation; Epitopes; Epitopes, T-Lymphocyte - immunology; Genes, MHC Class II; Histocompatibility antigen HLA; HIV; Human immunodeficiency virus; Human populations; Humans; Immunization; Immunodominance; Infectious diseases; Laboratory animals; Lymphocytes; Lymphocytes T; Macaca mulatta; Major histocompatibility complex; Mice; Mice, Inbred BALB C; Mice, Transgenic; Multiple HLA-binding epitopes; Peptides; Population; Populational vaccine; Primates; Redundancy; Rhesus macaques; T cell epitope; Transgenic mice; Vaccines; Viral diseases; Viral infections
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2021.11.076

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.