title: Loss of long term protection with the inclusion of HIV pol to a DNA vaccine encoding gag.
abstract: Traditional vaccine strategies that induce antibody responses have failed to protect against HIV infection in clinical trials, and thus cell-mediated immunity is now an additional criterion. Recent clinical trials that aimed to induce strong T cell responses failed to do so. Therefore, to enhance induction of protective T cell responses, it is crucial that the optimum antigen combination is chosen. Limited research has been performed into the number of antigens selected for an HIV vaccine. This study aimed to compare DNA vaccines encoding either a single HIV antigen or a combination of two antigens, using intradermal vaccination of C57BL/6 mice. Immune assays were performed on splenocytes, and in vivo protection was examined by challenge with a chimeric virus, EcoHIV, able to infect mouse but not human leukocytes, at 10 days (short term) and 60 days (long term) post final vaccination. At 60 days there was significantly lower frequency of induced antigen-specific CD8(+) T cells in the spleens of pCMVgag-pol-vaccinated mice compared with mice which received pCMVgag only. Most importantly, short term viral control of EcoHIV was similar for pCMVgag and pCMVgag-pol-vaccinated mice at day 10, but only the pCMVgag-vaccinated significantly controlled EcoHIV at day 60 compared with pCMV-vaccinated mice, showing that control was reduced with the inclusion of the HIV pol gene.
authors.affiliation: Virology Laboratory, Basil Hetzel Institute, Department of Surgery, University of Adelaide, Adelaide, Australia. Electronic address: tamsin.garrod@adelaide.edu.au.
authors.forename: Tamsin J
authors.initials: TJ
authors.lastname: Garrod
authors.affiliation: Virology Laboratory, Basil Hetzel Institute, Department of Surgery, University of Adelaide, Adelaide, Australia.
authors.forename: Tessa
authors.initials: T
authors.lastname: Gargett
authors.affiliation: Virology Laboratory, Basil Hetzel Institute, Department of Surgery, University of Adelaide, Adelaide, Australia.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Yu
authors.affiliation: Inflammation Biology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Lee
authors.initials: L
authors.lastname: Major
authors.affiliation: School of Molecular Biosciences, University of Adelaide, Adelaide, Australia.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Burrell
authors.affiliation: South Australian Health and Medical Research Institute, Adelaide, Australia.
authors.forename: Steven
authors.initials: S
authors.lastname: Wesselingh
authors.affiliation: Inflammation Biology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Suhrbier
authors.affiliation: Virology Laboratory, Basil Hetzel Institute, Department of Surgery, University of Adelaide, Adelaide, Australia.
authors.forename: Branka
authors.initials: B
authors.lastname: Grubor-Bauk
authors.affiliation: Virology Laboratory, Basil Hetzel Institute, Department of Surgery, University of Adelaide, Adelaide, Australia.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Gowans
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D015488:HIV Antigens; D014612:Vaccines; D054301:gag Gene Products, Human Immunodeficiency Virus; D054302:pol Gene Products, Human Immunodeficiency Virus
keywords: DNA vaccine; EcoHIV challenge; HIV