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J Virol. Evaluation of recombinant influenza-SIV vaccines in macaques.

Giuseppe

Emeritus
J Virol. 2009 May 13. [Epub ahead of print]

Evaluation of recombinant influenza-SIV vaccines in macaques.

Sexton A, De Rose R, Reece JC, Alcantara S, Loh L, Moffat JM, Laurie K, Hurt A, Doherty PC, Turner SJ, Kent SJ, Stambas J. - Department of Microbiology and Immunology, University of Melbourne, 3010, Australia; WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory, North Melbourne, 3051, Australia.

There is an urgent need for HIV vaccines that induce robust mucosal immunity. Influenza A viruses (both H1N1 and H3N2) were engineered to express SIV CD8 T cell epitopes and evaluated following administration to the respiratory tract of 11 pigtail macaques. Influenza virus was readily detected from respiratory tract secretions although the infections were asymptomatic. Animals seroconverted to influenza virus and generated CD8 and CD4 T cell responses to influenza virus proteins. SIV-specific CD8 T cell responses bearing the mucosal homing marker beta7 integrin were induced by vaccination of na?ve animals.
Further, SIV-specific CD8 T cell responses could be boosted by recombinant influenza-SIV vaccination of animals with already established SIV infection. Sequential vaccination with influenza-SIV recombinants of different subtypes (H1N1 followed by H3N2 or vice versa) produced only a limited boost in immunity, probably reflecting T cell immunity to conserved internal proteins of influenza A virus.
SIV challenge of macaques vaccinated with an influenza virus expressing a single SIV CD8 T cell resulted in a large anamnestic recall CD8 T cell response but immune escape rapidly ensued and there was no impact on chronic SIV viremia. Although our results suggest influenza-HIV vaccines hold promise for the induction of mucosal immunity to HIV, broader antigen cover will be needed to limit CTL escape.

PMID: 19439474 [PubMed - as supplied by publisher]

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