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Journal of Virology, October 2001, p. 8899-8908, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.8899-8908.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Hyperattenuated Recombinant Influenza A Virus Nonstructural-Protein-Encoding Vectors Induce Human Immunodeficiency Virus Type 1 Nef-Specific Systemic and Mucosal Immune Responses in Mice

Boris Ferko,* Jana Stasakova, Sabine Sereinig, Julia Romanova, Dietmar Katinger, Brigitte Niebler, Hermann Katinger, and Andrej Egorov

Institut für Angewandte Mikrobiologie, Universität für Bodenkultur, A-1190 Vienna, Austria

Received 20 March 2001/Accepted 22 June 2001

We have generated recombinant influenza A viruses belonging to the H1N1 and H3N2 virus subtypes containing an insertion of the 137 C-terminal amino acid residues of the human immunodeficiency virus type 1 (HIV-1) Nef protein into the influenza A virus nonstructural-protein (NS1) reading frame. These viral vectors were found to be genetically stable and capable of growing efficiently in embryonated chicken eggs and tissue culture cells but did not replicate in the murine respiratory tract. Despite the hyperattenuated phenotype of influenza/NS-Nef viruses, a Nef and influenza virus (nucleoprotein)-specific CD8+-T-cell response was detected in spleens and the lymph nodes draining the respiratory tract after a single intranasal immunization of mice. Compared to the primary response, a marked enhancement of the CD8+-T-cell response was detected in the systemic and mucosal compartments, including mouse urogenital tracts, if mice were primed with the H1N1 subtype vector and subsequently boosted with the H3N2 subtype vector. In addition, Nef-specific serum IgG was detected in mice which were immunized twice with the recombinant H1N1 and then boosted with the recombinant H3N2 subtype virus. These findings may contribute to the development of alternative immunization strategies utilizing hyperattenuated live recombinant influenza virus vectors to prevent or control infectious diseases, e.g., HIV-1 infection.

* Corresponding author. Mailing address: Institute of Applied Microbiology, Muthgasse 18B, A-1190 Vienna, Austria. Phone: 43/1 36006-6593 Fax: 43/1 36006-1249. E-mail: b.ferko{at}iam.boku.ac.at.

Journal of Virology, October 2001, p. 8899-8908, Vol. 75, No. 19
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.19.8899-8908.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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