Broadening of the T-cell repertoire to HIV-1 Gag p24 by vaccination of HLA-A2/DR transgenic mice with overlapping peptides in the CAF05 adjuvant

• Published in: PloS one Vol. 8; no. 5; p. e63575
• Main Authors: Korsholm, Karen S, Karlsson, Ingrid, Tang, Sheila T, Brandt, Lea, Agger, Else Marie, Aagaard, Claus, Andersen, Peter, Fomsgaard, Anders
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17-05-2013; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; AIDS vaccines; AIDS Vaccines - immunology; Amino Acid Sequence; Analysis of Variance; Animals; Antigenic determinants; Antigens; Biocompatibility; Biology; CD4 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cytotoxicity; Dendritic cells; Enzyme-Linked Immunosorbent Assay; Enzyme-Linked Immunospot Assay; Epitopes; Epitopes, T-Lymphocyte - immunology; Gag protein; Genetic engineering; Health aspects; Histocompatibility antigen HLA; Histocompatibility antigens; HIV; HIV (Viruses); HIV Core Protein p24 - genetics; HIV Core Protein p24 - immunology; HIV-1 - immunology; HLA histocompatibility antigens; HLA-A2 Antigen - genetics; Human immunodeficiency virus; Immune response; Immune response (cell-mediated); Immunity, Cellular - immunology; Immunology; Infectious diseases; Leukocytes; Lymphocytes; Lymphocytes T; Medicine; Mice; Mice, Transgenic; Molecular Sequence Data; p24 Protein; Peptides; Proteins; T cell receptors; T cells; Toxicity; Transgenic animals; Transgenic mice; Vaccination; Vaccines; Virology; Viruses; Denmark
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0063575

Induction of broad T-cell immune responses is regarded as critical for vaccines against the human immunodeficiency virus type 1 (HIV-1) which exhibit high diversity and, therefore, focus has been on inducing cytotoxic CD8 T-cell responses against the more conserved parts of the virus, such as the Gag protein. Herein, we have used the p24 protein which contains a range of conserved T-cell epitopes. We demonstrate that a vaccine of HIV-1 subtype B consensus group-specific antigen (Gag) p24 protein with the CD8-inducing liposomal cationic adjuvant formulation (CAF) 05, induces both CD4 and CD8 T-cell responses in CB6F1 mice. The adjuvanted vaccine also induced functional antigen-specific cytotoxicity in vivo. Furthermore, we found that when fragmenting the Gag p24 protein into overlapping Gag p24 peptides, a broader T-cell epitope specificity was induced in the humanized human leukocyte antigen (HLA)-A2/DR-transgenic mouse model. Thus, combining overlapping Gag p24 peptides with CAF05 appears to be a promising and simple strategy for inducing broader T-cell responses to multiple conserved epitopes which will be relevant for both prophylactic and therapeutic HIV-1 vaccines.