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. Less is known about the use of negative-stranded RNA viruses, whose genomes have been refractory to direct genetic manipulation. Using a recently described reverse genetics method, we investigated whether influenza 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 immunodeficiency virus type 1 (HIV-1) MN. This peptide was inserted into the loop 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 were 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 specifically recognize the HIV sequence. These results suggest that influenza virus can be used as an expression vector for inducing both B- and T-cell-mediated immunity against other infectious agents.
Li
S
S
Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029.
Polonis
V
V
Isobe
H
H
Zaghouani
H
H
Guinea
R
R
Moran
T
T
Bona
C
C
Palese
P
P
D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000276:immunology; D001483:Base Sequence; D017931:DNA Primers; D000939:Epitopes; D015483:HIV Antibodies / Q000096:biosynthesis*; D015488:HIV Antigens / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D006389:Hemagglutinins, Viral / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
D000914:Antibodies, Viral; D017931:DNA Primers; D000939:Epitopes; D015483:HIV Antibodies; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D006389:Hemagglutinins, Viral; D014614:Vaccines, Synthetic