CHIMERIC INFLUENZA-VIRUS INDUCES NEUTRALIZING ANTIBODIES AND CYTOTOXIC T-CELLS AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

Expression vectors based on DNA or plus-stranded RNA viruses are being developed as vaccine carriers directed against various pathogens. Les s is known about the use of negative-stranded RNA viruses, whose genom es have been refractory to direct genetic manipulation. Using a recent ly described reverse genetics method, we investigated whether influenz a virus is able to present antigenic structures from other infectious agents. We engineered a chimeric influenza virus which expresses a 12- amino-acid peptide derived from the V3 loop of gp120 of human immunode ficiency virus type 1 (HIV-1) MN. This peptide was inserted into the l oop of antigenic site B of the influenza A/WSN/33 virus hemagglutinin (HA). The resulting chimeric virus was recognized by specific anti-V3 peptide antibodies and a human anti-gp120 monoclonal antibody in both hemagglutination inhibition and neutralization assays. Mice immunized with the chimeric influenza virus produced anti-HIV antibodies which w ere able to bind to synthetic V3 peptide, to precipitate gp120, and to neutralize MN virus in human T-cell culture system. In addition, the chimeric virus was also capable of inducing cytotoxic T cells which sp ecifically recognize the HIV sequence. These results suggest that infl uenza virus can be used as an expression vector for inducing both B- a nd T-cell-mediated immunity against other infectious agents.