PMID- 23691069 OWN - NLM STAT- MEDLINE DCOM- 20131216 LR - 20240319 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 5 DP - 2013 TI - 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. PG - e63575 LID - 10.1371/journal.pone.0063575 [doi] LID - e63575 AB - 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. FAU - Korsholm, Karen S AU - Korsholm KS AD - Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark. FAU - Karlsson, Ingrid AU - Karlsson I FAU - Tang, Sheila T AU - Tang ST FAU - Brandt, Lea AU - Brandt L FAU - Agger, Else Marie AU - Agger EM FAU - Aagaard, Claus AU - Aagaard C FAU - Andersen, Peter AU - Andersen P FAU - Fomsgaard, Anders AU - Fomsgaard A LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20130517 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (AIDS Vaccines) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HIV Core Protein p24) RN - 0 (HLA-A2 Antigen) RN - 0 (p24 protein, Human Immunodeficiency Virus Type 1) SB - IM MH - AIDS Vaccines/*immunology MH - Amino Acid Sequence MH - Analysis of Variance MH - Animals MH - CD8-Positive T-Lymphocytes/*immunology MH - Enzyme-Linked Immunosorbent Assay MH - Enzyme-Linked Immunospot Assay MH - Epitopes, T-Lymphocyte/immunology MH - HIV Core Protein p24/genetics/*immunology MH - HIV-1/*immunology MH - HLA-A2 Antigen/genetics MH - Immunity, Cellular/*immunology MH - Mice MH - Mice, Transgenic MH - Molecular Sequence Data PMC - PMC3656914 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2013/05/22 06:00 MHDA- 2013/12/18 06:00 PMCR- 2013/05/17 CRDT- 2013/05/22 06:00 PHST- 2012/12/21 00:00 [received] PHST- 2013/04/04 00:00 [accepted] PHST- 2013/05/22 06:00 [entrez] PHST- 2013/05/22 06:00 [pubmed] PHST- 2013/12/18 06:00 [medline] PHST- 2013/05/17 00:00 [pmc-release] AID - PONE-D-12-40566 [pii] AID - 10.1371/journal.pone.0063575 [doi] PST - epublish SO - PLoS One. 2013 May 17;8(5):e63575. doi: 10.1371/journal.pone.0063575. Print 2013.