DNA vaccines encoding membrane-bound or secreted forms of heat shock protein 70 exhibit improved potency

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

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Traditional vaccine strategies are inefficient against challenge with complex pathogens including HIV; therefore, novel vaccine technologies are required. DNA vaccines are attractive as they are relatively cheap and easy to manufacture, but a major limitation has been their lack of immunogenicity in humans, which may be overcome with the incorporation of an adjuvant. HSP70 is a recognised damage-associated molecular pattern, which is a potential adjuvant. We investigated the immunogenicity of a DNA vaccine encoding HIV gag and HSP70; the latter was genetically modified to produce cytoplasmic, secreted or membrane-bound HSP70, the expression of which was controlled by an independent promoter. The DNA was administered to C57BL/6 mice to evaluate gag-specific T-cell responses. Our results demonstrated the ability of membrane-bound and secreted HSP70 to significantly enhance gag-specific T-cell responses and increase the breadth of T-cell responses to include subdominant epitopes. Membrane-bound or secreted HSP70 also significantly improved the multifunctionality of HIV-specific T cells and T-cell proliferation, which is important for maintaining T-cell integrity. Most importantly, the inclusion of membrane-bound HSP70, secreted HSP70 or a combination significantly increased protection in mice challenged with EcoHIV, a chimeric virus that replicates in mouse leukocytes in vivo.

Original languageEnglish
Pages (from-to)1992-2002
Number of pages11
JournalEuropean Journal of Immunology
Volume44
Issue number7
DOIs
Publication statusPublished or Issued - Jul 2014

Keywords

  • Adjuvant
  • DNA vaccines
  • HSP70

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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