Live attenuated influenza virus expressing human interleukin-2 reveals increased immunogenic potential in young and aged hosts.
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.
Ferko
Boris
B
Institute of Applied Microbiology, University of Natural Resources and Applied Life Sciences, Muthgasse 18B, A-1190 Vienna, Austria. .
Kittel
Christian
C
Romanova
Julia
J
Sereinig
Sabine
S
Katinger
Hermann
H
Egorov
Andrej
A
D000818:Animals; D002522:Chlorocebus aethiops; D003673:Defective Viruses / Q000276:immunology*; D006801:Humans; D007109:Immunity / Q000187:drug effects* / Q000276:immunology; D007114:Immunization; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D014613:Vaccines, Attenuated / Q000008:administration & dosage* / Q000627:therapeutic use; D014709:Vero Cells
D007252:Influenza Vaccines; D007376:Interleukin-2; D014613:Vaccines, Attenuated