Chimeric influenza viruse expressing truncated forms of HIV-1 GP41 protein

Research project P 13715 Chimeric Influenza/GP41 Viruses Andrej Yu. EGOROV 28.06.1999 There is evidence that neutralizing antibodies protect against HIV infection in certain animal models. One of the main problems in the development of HIV vaccines concerns the poor immunogenicity of the mature oligomeric glycoprotein complex that constitutes the surface spikes of HIV virions. One possible way to improve the antigenic presentation of envelope structures is their expression in modified (e.g. truncated) forms by an appropriate viral vector. In this manner sites that are important for neutralization of the HIV-1 might be better presented to the immune system. We recently succeeded in establishing a reverse genetics method for the nonstructural gene (NS gene) of influenza A virus, which allows us to insert rather long foreign sequences into the NS1 protein. Currently rescued chimeric influenza viruses, containing up to 150 amino-acids insertions, displayed normal growth characteristics in tissue culture, embryonated eggs and respiratory tract of mice. Our goal now is to use this new technology to generate a set of stable influenza virus vectors expressing full length as well as several truncated forms of HIV-1 gp-41 protein. In contrast to the highly variable gp120 molecules gp41 shows a high degree of conservativity. Some epitopes involved in neutralization of a variety of primary HIV-1 isolates are mapped within conserved sequences of gp-41 subunit. We will immunize mice and macaques intranasaly and determine the specific humoral systemic and mucosal immune responses with emphasis on the induction of HIV-1 neutralizing antibody responses against primary HIV-1 isolates.