Abstract
Background: DNA vaccines encoding conserved antigens of influenza A virus can induce broad cross-protection against multiple influenza A subtypes. Better understanding of the mechanisms of this protection can help guide vaccine development. Methods: Mice were vaccinated with plasmids expressing nucleoprotein (NP) and matrix (M) given i.m., followed by lethal i.n. challenge with influenza virus. CTL were analyzed by 51Cr-release using fresh lung lymphocytes. Results: A/NP+A/M vaccination promoted viral clearance and led to recovery, at challenge virus doses that were lethal to controls. CD8+ CTL were induced and were highly specific for influenza A antigens, but were not required for protection. Depletion of both CD4+ and CD8+ T cells during the challenge period abrogated protection. A plasmid expressing influenza B/NP was used to demonstrate specificity of antibodies produced and of protection against influenza B vs. A challenge. Discussion: DNA vaccination gave protection corresponding to the influenza A vs. B inserted genes, confirming immunological specificity. For A/NP+A/M DNA, T cells are required, but either CD4+ or CD8+ T cells protected in the absence of the other subset. These findings about DNA vaccines encoding antigens conserved among viral subtypes can be applied to human vaccine development for protection against new pandemic viruses.
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