HIV VACCINE THERAPY

The immunoregulatory mechanisms responsible for effective the in vivo post-infection control of HIV are unknown. In the setting of natural HIV infection, host-directed immune responses directed against gp120 are minimal. This includes poor gp120 epitope specific antibody responses to C1, C2 and C3; lack of T-cell recognition and proliferation to gp120; and minimal envelope cytotoxic T-cell responses. The historical important of anti-envelope responses in the control of other viral pathogens, coupled with the paucity of anti-envelope responses elicited as a consequence of HIV infection, formed the basis for our rationale to pursued a research program which focused on post-infection vaccination utilizing HIV enveloped derived products. Recently we have demonstrated the scientific feasibility of post-infection vaccination with an HIV envelope based vaccine to broaden host-directed HIV-specific immune responses to include seroconversion to gp120 C1, C2 and C3; the induction of T-cell recognition to gp160; and cytotoxic T-cell responses to envelope peptides. The in vivo safety and immunogenicity of the product in adult patients with early HIV infection has been demonstrated. An expanded phase II trial with rgp160 (MGS) is ongoing to examine the potential role of HIV-specific vaccine therapy to alter the natural history of HIV infection. Finally, we are exploring the value of post-infection immunization in defining specific immune responses and their in vivo HIV immunoregulatory relevance.