Drug Discov Ther. 2009;3(6):252-259.

Induction of immune responses to a human immunodeficiency virus type 1 epitope by novel chimeric influenza viruses.

Takizawa N, Morita M, Adachi K, Watanabe K, Kobayashi N

Mucosal and systemic immune responses play an important role in the prevention of infections, including infection with human immunodeficiency virus type 1 (HIV-1). Influenza virus can efficiently induce mucosal and systemic immune responses, and thus, chimeric influenza viruses expressing the peptides derived from HIV-1 proteins have been generated to elicit immune responses against the inserted peptide. Novel chimeric influenza viruses were generated with full length of the V3-loop of gp120 or cytotoxic T-lymphocyte epitope of gag from HIV-1 inserted into the stalk of NA (NA-V3 and NA-gag, respectively) and the V3-loop was inserted into the intracellular domain of M2 (M2-V3). The immune responses of mice infected with these chimeric influenza viruses were investigated. The intranasal infection of NA-gag induced gag epitopespecific CTLs and the intranasal infection of NA-V3 and M2-V3 induced V3-specific antibodies. The serum from mice infected with NA-V3 neutralized a clinical isolate of HIV-1 and the infection of NA-V3 induced V3-specific secretory antibodies. These results suggest that intranasal infection of these chimeric influenza viruses could induce both humoral and cellular immune responses against an inserted foreign peptide and therefore could be a potential candidate for use as an HIV-1 vaccine.

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