Immunomodulatory activity of 2-deoxyguanosine nanoparticles in DNA vaccines

Abstract

Abstract DNA vaccines induce protective immune responses against several pathogens and tumor cells, but strategies to improve their effectiveness are still under study. Only two adjuvants have been licensed by the FDA, which increases the needs for the discovery of novel adjuvants for HIV vaccines and other infectious diseases. In this regard, we study the immunomodulatory properties of 2-Deoxyguanosine-based nanoparticles (SHS) in DNA vaccines coding for HIV Gag (NL4-3 clone) and Vaccinia Virus Western Reserve (VVWR) A27 proteins. The sequence of A27L was codon optimized and linked to the Outer Domain-1 (OD1) of gp120 HIV-1 protein sequence serving as an additional molecular adjuvant. In this study, female Balb/c mice were immunized three times intramuscularly with plasmids (pGag and pOD1-A27L). Then, seven days after the last dose, cellular and humoral immunity were evaluated through ELISpot and ELISA assays. We found significantly higher frequencies of IFN-γ-producing cells in mouse immunized with pGag and pOD1-A27L co-formulated with SHS versus controls. We also found higher significant levels of IFN-γ over IL-4 in supernatant of splenocytes isolated from mice receiving pGag and pOD1-A27L combined with SHS. Moreover, administration of pOD1-A27L+SHS stimulated a significant higher production of total IgG in mice when compared to Naïve group. Here, we demonstrated that pGag and pOD1-A27L vaccines co-formulated with SHS nanoparticles successfully activate adaptive immunity through production of Th-1 cytokines and/or IgG antibodies. As this type of immunity is essential to clear many viral infections, these data support the evaluation of SHS nanoparticles as a novel adjuvant for DNA vaccines against multiple viral infectious agents.