Alireza Milani, Azam Bolhassani: A novel endogenous adjuvant for development of therapeutic vaccine against HIV-1 infection. The 14th International Congress of Immunology & Allergy, Tehran-Iran; 04/2018. (Oral)
Background: Vaccination is currently considered as an additional therapeutic approach to stimulate HIV-specific immune responses. In order to development of an effective vaccine against HIV-1 infection, novel vaccine strategies are required. Promising results of DNA-based, protein-based and heterologous prime/boost-based strategies showed their influence on eliciting both humoral and cellular immune responses. Recently, the endogenous adjuvants such as heat shock proteins (HSPs) have been suggested effectively to induce antigen-specific humoral and cellular immune responses.
Methods: The recombinant HIV-1 Nef, and Nef fused to Hsp27 DNA and also protein constructs were generated in eukaryotic and prokaryotic expression systems, respectively. Mice were immunized with these constructs based on three strategies of DNA/DNA, Protein/protein and DNA/Protein. To determine the induction of immune response, sera and splenocytes were analyzed for humoral and cellular responses, respectively.
Results: Analysis of the immune responses indicated that the Hsp27-Nef fusion protein significantly increased the Nef-specific T cell responses. Indeed, this regimen induced high levels of IgG2a and IFN-γ directed toward Th1 responses and also Granzyme B secretion compared to other immunization strategies. Moreover, the immunostimulatory properties of Freund’s adjuvant were significantly less than Hsp27 in different immunization strategies.
Conclusion: These data demonstrated that the use of Hsp27 in protein-based strategy could improve HIV-1 Nef-specific B- and T-cell immune responses as a promising HIV-1 vaccine candidate in future.
Keywords: Therapeutic HIV vaccine, Nef, Endogenous adjuvant, Small heat shock protein 27
