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DNA and recombinant virus vaccines against swine influenza virus (SIV) have been pursued with promising results, but induce poor immunogenicity. This study evaluated the effects of a vaccine regimen inmice including priming with three DNA vaccines expressing soluble HA (sHA), complete HA (tmHA), orsHA fused with three copies murine C3d (sHA-mC3d3) and boosting with recombinant pseudorabiesvirus expressing HA (rPRV-HA). Immune responses were monitored by ELISA, HI assays, and virus neutralization. Protective efficacy was evaluated by virus isolation from lungs, distribution in tissues, and pathology following challenge with H3N2 SIV. Priming with sHA-mC3d3 and boosting with rPRV-HAinduced higher levels of HA-specific antibodies and yielded the most effective protection. This findingimplied that priming with a DNA vaccine expressing C3d fused with antigen and boosting with a recombinant vector vaccine is an effective way to induce protective bumoral immunity and prevent some infectious diseases.