Enhancement of the efficiency of a DNA vaccine construct harboring HSP70 mini-chaperones linked to HIV-1 Nef antigen using IL-7 cytokine and REV peptide.

Interleukin-7 (IL-7) is essential for the proliferation and maintenance of T lymphocytes, suggesting its potential role as an adjuvant to enhance vaccine efficacy. Furthermore, truncated domains from the amino- or carboxyl-termini of heat shock proteins (HSPs), termed mini-chaperones, are capable of augmenting antigen-targeted T lymphocyte activation in the context of pathogen infections. Additionally, the REV peptide derived from HIV-1 Rev protein was reported to function as a cell-penetrating peptide for the delivery of plasmid DNA. Herein, we assessed the potential of distinct HSP70 domains, along with IL-7 and the REV peptide, to amplify immune responses directed against the HIV-1 Nef antigen and to maintain cytokine secretion against single-cycle HIV-1 (SCR) variant. Our findings revealed that the combination of pVAX-CT-HSP70-Nef with pVAX-IL-7 could significantly increase Th1 and CTL activities through elevated secretion of IFN-γ and Granzyme B compared to other groups, and markedly stimulate IFN-γ production in response to HIV-1 SCR variant. Furthermore, delivery of pVAX-CT-HSP70-Nef combined with pVAX-IL-7 by the REV peptide could substantially increase Granzyme B secretion, boost antigen-specific cellular immune responses, and augment anti-HIV-1 SCR effects through elevated secretion of IFN-γ. Therefore, this vaccination approach holds strong potential as a therapeutic candidate for controlling HIV-1 infection.