1 Infectious Diseases, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU2 Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.3 unknown4 Infectious Diseases, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU
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.
Plos One, 2013, Vol 8, Issue 5
AIDS Vaccines; Amino Acid Sequence; Analysis of Variance; Animals; CD8-Positive T-Lymphocytes; Enzyme-Linked Immunosorbent Assay; Enzyme-Linked Immunospot Assay; Epitopes, T-Lymphocyte; HIV Core Protein p24; HIV-1; HLA-A2 Antigen; Immunity, Cellular; Mice; Mice, Transgenic; Molecular Sequence Data