Adjuvant Action of MurineIL-2/IgPlasmid After Intramuscular Immunization With Indian HIV-1 Subtype C Recombinantenv.gp120 Construct

Abstract

The human immunodeficiency virus (HIV) epidemic is probably the greatest scourge to affect mankind in the 20th century. Containment of the acquired immunodeficiency syndrome (AIDS) epidemic will require an effective vaccine. Of various vaccine approaches, immunization with DNA plasmids containing HIV-1 structural genes is the most popular approach. However, an important limitation of DNA immunization is that these responses are relatively weak and are often only transient in their nature. The use of immunologic adjuvants together with DNA vaccines is a promising way to enhance and to optimize DNA-derived immunity. Cytokines have been widely used to enhance the immune responses of DNA vaccines. In the present investigation, we studied the in vivo immunomodulation of HIV-1 Indian subtype C plasmid construct (pJWSK3, encoding envgp120 gene) by plasmid-based murine IL-2/Ig construct. Subcloning of mIL-2/Ig gene from pVRCmIL-2/Ig construct into pJW4304 vector was done followed by its in vitro expression study on the COS-7 cell line. Co-immunization of the recombinant HIV-1 env-gp120 construct with the IL-2/Ig construct in the female Balb/c mice by the intramuscular route resulted in induction of significantly higher levels of both HIV-1-specific antibody response and cell mediated immune response than by DNA plasmid construct alone (p < 0.001 and p < 0.05, respectively). The induced HIV-1-specific murine IFN-gamma response was robust, broad based, and seen even at the end of 6 months after immunization. Taken together these results indicate that the strategy of using IL-2/Ig plasmid can be highly effective when used along with recombinant DNA constructs and serve as the potential tool for the development of more rationally designed vaccines against HIV-1.