DNA IMMUNIZATION WITH A BOVINE ROTAVIRUS VP4 GENE INDUCES A TH1-LIKE IMMUNE-RESPONSE IN MICE

Immunization with naked plasmid DNA effectively induces both humoral a nd cell-mediated immunity to vaccine antigens and can confer protectio n against numerous infectious diseases. To explore the potential use o f DNA immunization to induce rotavirus-specific immune responses, we u sed plasmid DNA encoding the VP4 gene of bovine rotavirus (BRV). Intra smuscular injection of the plasmid encoding the VP4 gene into C57BI/6 mice induced cell-mediated immunity as measured by cytokine production . Although DNA immunization did not induce a detectable BRV-specific a ntibody response, DNA-immunized animals were primed for antibody produ ction and a cellular immune response. Following viral inoculation, the immunized animals displayed an enhanced number of BRV-specific antibo dy-secreting cells and cytotoxic activity. The immune response induced by DNA immunization alone or followed by viral inoculation was biased toward IFN-gamma production (Th1-like). CD4+ lymphocytes were the maj or source of IFN-gamma production in the spleen following DNA immuniza tion. In contrast, a balanced cytokine production was observed in the spleens of animals receiving whole virus. These experiments showed tha t DNA immunization with a gene encoding the VP4 protein of BRV stimula ted a Th1-like immune response in mice, and this bias in the immune re sponse persisted following exposures to whole virus.