Chimeric influenza virus induces neutralizing antibodies and cytotoxic T cells against human immunodeficiency virus type 1

Abstract

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 gpl20 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-gpl20 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 gpl20, 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 Band T-cell-mediated immunity against other infectious agents.

Attributes of Glycosylation in the Establishment of the Unfolding Pathway of Soybean Agglutinin

“…In many instances, glycosylation is seen to have a remarkable effect in attaining the final functional fold of the protein, whereas in others it is seen to have little or no effect on the ultimate state of the protein. For example, the HIV 1 gp-120 protein fails to reach its final folded state in the absence of glycosylation, whereas the nonglycosylated RNase A has lower folding rates compared to its glycosylated counterpart, RNase B (10)(11)(12).Usually, glycans do not generate permanent secondary structure but trigger local conformational alterations close to the glycosylation site, particularly by inducing a b-turn at the site (13).…”

Expression of Foreign Proteins by Poliovirus Polyprotein Fusion: Analysis of Genetic Stability Reveals Rapid Deletions and Formation of Cardioviruslike Open Reading Frames

“…Many attempts have been made to manipulate the genomes of RNA viruses so that they can function as expression vectors. Among these RNA viruses are Sindbis virus (8,48,51), Semliki Forest virus (31), influenza virus (19,30), tobacco etch virus (16), mengovirus (2,3), and poliovirus (PV) (1,6,9,10,12,14,22,23,32,35,36,38,44).…”

Recombinant Vectors as Influenza Vaccines

“…Chimeric influenza viruses have been developed to express HIV epitopes. After intranasal administration, these vectors induce a long-lasting mucosal antibody response in not only the respiratory tract, but also the genital tract (Li et al 1993;Muster et al 1994Muster et al , 1995Palese et al 1997;Gonzalo et al 1999;Gherardi et al 2003;Nakaya et al 2003). The encouraging results obtained using influenza virus vectors thus far demonstrate the need for further research in this field.…”