IN-VIVO PROTECTIVE ANTI-HIV IMMUNE-RESPONSES IN NONHUMAN-PRIMATES THROUGH DNA IMMUNIZATION

An effective immune response involves the specific recognition of and elimination of an infectious organism at multiple levels. In this cont ext DNA immunization can present functional antigenic proteins to the host for recognition by all arms of the immune system, yet provides th e opportunity to delete any genes of the infectious organism which cod e for antigens or pieces of antigens that may have deleterious effects . Our group has developed the use of nucleic acid immunization as a po ssible method of vaccination against Human immunodeficiency virus type 1 (HIV-1) [1,2,3,10,11,12]. Sera from non-human primates immunized wi th DNA vectors that express the envelope proteins from HIV-1 contain a ntibodies specific to the HIV-1 envelope. These sera also neutralize H IV-1 infection in vitro and inhibit cell to cell infection in tissue c ulture. Analysis of cellular responses is equally encouraging. T cell proliferation as well as cytotoxic T cell lysis of relevant env expres sing target cells were observed. In addition, evidence that DNA vaccin es are capable of inducing a protective response against live virus wa s demonstrated using a chimeric SIV/HIV (SHIV) challenge in vaccinated cynomologous macaques. We found that nucleic acid vaccination induced protection from challenge in one out of four immunized cynomolgus mac aques and viral load was lower in the vaccinated group of animals vers us the control group of animals. These data encouraged us to analyze t his vaccination technique in chimpanzees, the most closely related ani mal species to man. We observed the induction of both cellular and hum oral immune responses with a DNA vaccine in chimpanzees. These studies demonstrate the utility of this technology to induce relevant immune responses in primates which may ultimately lead to effective vaccines.