This research program is investigating questions concerning immune responses, with a focus on protective immunity to viral infections. Main projects: 1. Antibody responses to different forms of CD4: Reactivity of antibodies with recombinant gp120 versus cell surface expressed HIV envelope was studied due to implications about vaccines under study. A panel of mAbs to gp120 will be made available to the research community via repository distribution. 2. Mechanisms of protective immunity to influenza virus infection: Of the immune effectors induced by vaccines or infection, an interplay of host and viral factors determine which actually provide protection against infection. We are studying several situations, to analyze whether antibody or cell-mediated immunity is responsible for protection: a) Heterosubtypic immunity: protection by prior infection with one subtype of influenza A virus against challenge with another subtype. Experiments are assessing the roles of T cell subsets and of antibodies. Results may help us understand the limitations of existing vaccines, as well as how to modify them. b) Vaccination with plasmid DNA. We are studying validation of the method of immunization using plasmid DNA. Immune effectors mediating protection are being analyzed. Results will help us understand responses to plasmids, which are in clinical trials for cancer therapy and gene therapy. c) Immunization of b2-microglobulin deficient mice. These mice were shown to make lower than normal antibody responses, but for reasons that are unclear and under investigation. Analysis of this question will help us understand efficacy of licensed vaccines in immunodeficient individuals.