Acquired immunodeficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV) is known as a threat to human health due to ineffective treatment, drug resistance, and also side effects. Therefore, designing an efficient immunogenic construct to eliminate this infection is very important. Among therapeutic vaccines, protein- and nucleic acid-based vaccines have been widely used as a therapeutic agent against various infectious diseases. Among HIV-1 proteins, Nef protein has several roles in the early stages of virus replication leading to the development of this infection, and thus this protein could be a suitable candidate antigen for vaccine design. An important issue in protein vaccine design is the use of an effective adjuvant for increasing vaccine immunity as well as the selection of a suitable antigen. In this regard, molecular chaperones including heat shock proteins have attracted a special interest. Heat shock proteins have been used as a natural and safe adjuvant for vaccine development in preclinical and clinical trials. The studies showed that heat shock proteins such as HSP70 and HSP27 could deliver antigens by interacting with the surface receptors on antigen-presenting cells. Regarding the expression of both HSP70 and HSP27 increases in stress conditions, and these HSPs cooperate in biochemical functions such as cell apoptosis, and also induce antigen-specific immune responses, thus in this study, adjuvant effects of HSP70 and HSP27 will be compared to increase immune response against HIV-1 Nef antigen for the first time. Some studies showed that the N-terminal and especially the C-terminal fragments of HSP70 possess the same effects with the full length of HSP70; thus in this study, both fragments linked to Nef protein will be utilized. Moreover, mice immunization will be performed by heterologous DNA prime/ protein boost strategy. After determination of the most effective heat shock protein (HSP27, N-HSP70 and C-HSP70) in stimulation of humoral and cellular immune responses, it will be used to evaluate protective effects against HIV-1 infections.
