title: 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.
abstract: 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.
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Korsholm
authors.forename: Ingrid
authors.initials: I
authors.lastname: Karlsson
authors.forename: Sheila T
authors.initials: ST
authors.lastname: Tang
authors.forename: Lea
authors.initials: L
authors.lastname: Brandt
authors.forename: Else Marie
authors.initials: EM
authors.lastname: Agger
authors.forename: Claus
authors.initials: C
authors.lastname: Aagaard
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.forename: Anders
authors.initials: A
authors.lastname: Fomsgaard
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D000704:Analysis of Variance; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D016655:HIV Core Protein p24 / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000235:genetics; D007111:Immunity, Cellular / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D016655:HIV Core Protein p24; D015789:HLA-A2 Antigen; C514799:p24 protein, Human Immunodeficiency Virus Type 1