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GLOBHELS-Global helse

Novel vaccine candidates and delivery systems for HIV and influenza

Awarded: NOK 2.0 mill.

Aim: We wish to generate novel vaccines for important infectious diseases such as HIV (FRIBIOMOL)and influenza (GLOBVAC). 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 and DNA-mediated delivery systems, it is possible to generate novel types of recombinant vacc ines that target antigen presenting cells (APC) for efficient delivery of antigen and induction of strong immune responses. Vaccibodies: The PI (Bogen) has developed a novel vaccine molecules, called vaccibodies, that have given promising results in tum or immunology. We here wish to extend the vaccibody strategy to infectious disesease like HIV and flu. A premise for vaccibodies is that targeting of antigen to APC enhances immune responses. Vaccibodies are homodimers, each chain consisting of a "targeti ng 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/PI: generate vaccibodies tha t 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 immunogenicity. (ii) PhD student/PI: generate vaccibodi es that contain hemagglutinin (HA) as antigenic unit and MIP-1a as targeting unit. (iii) Postdoc/Vyas (India): develop nanoparticle-based delivery of DNA in aerosols to airways. Project plan: The postdocs and PhD student will work in Bogen and Vyas labs and will generate the vaccibodies/delivery systems. The postdoc and PhD student will visit Barouch and von Boehmer labs at Harvard to perform in vivo testing in mouse models.

Funding scheme:

GLOBHELS-Global helse