Loss of long term protection with the inclusion of HIV pol to a DNA vaccine encoding gag

Tamsin J. Garrod, Tessa Gargett, Wenbo Yu, Lee Major, Christopher J. Burrell, Steven Wesselingh, Andreas Suhrbier, Branka Grubor-Bauk, Eric J. Gowans

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

LanguageEnglish
Pages25-33
Number of pages9
JournalVirus Research
Volume192
DOIs
Publication statusPublished - 4 Nov 2014

Keywords

  • DNA vaccine
  • EcoHIV challenge
  • HIV

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases
  • Cancer Research

Cite this

Garrod, Tamsin J. ; Gargett, Tessa ; Yu, Wenbo ; Major, Lee ; Burrell, Christopher J. ; Wesselingh, Steven ; Suhrbier, Andreas ; Grubor-Bauk, Branka ; Gowans, Eric J. / Loss of long term protection with the inclusion of HIV pol to a DNA vaccine encoding gag. In: Virus Research. 2014 ; Vol. 192. pp. 25-33.
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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.",
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Garrod, TJ, Gargett, T, Yu, W, Major, L, Burrell, CJ, Wesselingh, S, Suhrbier, A, Grubor-Bauk, B & Gowans, EJ 2014, 'Loss of long term protection with the inclusion of HIV pol to a DNA vaccine encoding gag', Virus Research, vol. 192, pp. 25-33. https://doi.org/10.1016/j.virusres.2014.08.008

Loss of long term protection with the inclusion of HIV pol to a DNA vaccine encoding gag. / Garrod, Tamsin J.; Gargett, Tessa; Yu, Wenbo; Major, Lee; Burrell, Christopher J.; Wesselingh, Steven; Suhrbier, Andreas; Grubor-Bauk, Branka; Gowans, Eric J.

In: Virus Research, Vol. 192, 04.11.2014, p. 25-33.

Research output: Contribution to journalArticle

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