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Journal of Virology, December 2006, p. 11621-11627, Vol. 80, No. 23
0022-538X/06/$08.00+0     doi:10.1128/JVI.01645-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Live Attenuated Influenza Virus Expressing Human Interleukin-2 Reveals Increased Immunogenic Potential in Young and Aged Hosts{triangledown}

Boris Ferko,{dagger} Christian Kittel,{dagger}* Julia Romanova, Sabine Sereinig, Hermann Katinger, and Andrej Egorov

Institute of Applied Microbiology, University of Natural Resources and Applied Life Sciences, Muthgasse 18B, A-1190 Vienna, Austria

Received 1 August 2006/ Accepted 5 September 2006

Despite the reported efficacy of commercially available influenza virus vaccines, a considerable proportion of the human population does not respond well to vaccination. In an attempt to improve the immunogenicity of live influenza vaccines, an attenuated, cold-adapted (ca) influenza A virus expressing human interleukin-2 (IL-2) from the NS gene was generated. Intranasal immunization of young adult and aged mice with the IL-2-expressing virus resulted in markedly enhanced mucosal and cellular immune responses compared to those of mice immunized with the nonrecombinant ca parent strain. Interestingly, the mucosal immunoglobulin A (IgA) and CD8+ T-cell responses in the respiratory compartment could be restored in aged mice primed with the IL-2-expressing virus to magnitudes similar to those in young adult mice. The immunomodulating effect of locally expressed IL-2 also gave rise to a systemic CD8+ T-cell and distant urogenital IgA response in young adult mice, but this effect was less distinct in aged mice. Importantly, only mice immunized with the recombinant IL-2 virus were completely protected from a pathogenic wild-type virus challenge and revealed a stronger onset of virus-specific CD8+ T-cell recall response. Our findings emphasize the potential of reverse genetics to improve the efficacy of live influenza vaccines, thus rendering them more suitable for high-risk age groups.

* Corresponding author. Mailing address: Institute of Applied Microbiology, University of Natural Resources and Applied Life Sciences, Muthgasse 18B, A-1190 Vienna, Austria. Phone: 43-1-36006-6202. Fax: 43-1-3697615. E-mail: c.kittel{at}greenhillsbiotech.com.

{triangledown} Published ahead of print on 13 September 2006.

{dagger} B.F. and C.K. contributed equally to this work.

Journal of Virology, December 2006, p. 11621-11627, Vol. 80, No. 23
0022-538X/06/$08.00+0     doi:10.1128/JVI.01645-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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