Vaccine development for HIV and influenza

Aim: Based on the vaccibody principle developed by us, we wish to generate novel vaccines for important infectious diseases such as HIV and influenza. Background: Vaccination has had an enormous impact on health and longevity of humans world-wide. However , for some important diseases such as HIV, there are no available vaccines. For other diseases, there is a need for better vaccines (influenza). Based on recent advances in basic immunology, it is possible to generate novel types of recombinant vaccines that target antigen presenting cells for efficient delivery of antigen and induction of strong immune responses. Vaccibodies: We have developed a novel type of vaccine molecules, called vaccibodies, that have given very promising results as tumor vaccin es for mouse B cell lympomas and myelomas. We now wish to extend the vaccibody strategy to infectious disesease like HIV and flu. A premise for vaccibodies is that targeting of antigen to antigen presenting cells (APC) enhances immune responses. Vaccibodi es are homodimers, each chain consisting of a "targeting unit" that bind to APC, a "dimerization unit" consisting of immunoglobulin hinge+CH3 domain, and an "antigenic unit". A cassette vector allows rapid genetic construction of vaccibodies. Projects of the proposal: (i) Postdoc: to generate vaccibodies that contain gp120 from HIV as antigenic unit. Targeting unit will be MIP-1a chemokine which appears to facilitate cytotoxic CD8+ responses. A universal CD4+ T cell epitope will be integrated to enhance i mmunogenicity. (ii) PhD student: to generate vaccibodies that contain hemagglutinin (HA) as antigenic unit and MIP-1a as targeting unit. Project plan: The postdoc and PhD student will work in 20-member Bogen lab and will generate the novel vaccibodies d escribed above. The postdoc and PhD student will visit Barouch and von Boehmer labs in Boston to perform the in vivo testing in mouse models.