A suicidal DNA vaccine based on a Semliki Forest virus (SFV) replicon was evaluated for the development of a vaccine against swine vesicular disease virus (SVDV). The 1BCD gene of SVDV was cloned and inserted into pSCA1, an SFV DNA-based replicon vector. The resultant plasmid, pSCA/1BCD, was transfected into BHK-21 cells and the antigenicity of the expressed protein was confirmed using an indirect immunofluorescence assay. Immunogenicity was studied in guinea pigs and swine. Animals were injected intramuscularly three times with pSCA/1BCD at regular intervals. Anti-SVDV antibodies were detected by ELISA, the lymphocyte proliferation response was tested by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide method and neutralizing antibodies were measured by microneutralization tests. The data showed that SVDV-specific antibodies, neutralizing antibodies and lymphocyte proliferation were induced in both guinea pigs and swine. Furthermore, after three successive vaccinations with pSCA/1BCD, half of the pigs were protected against challenge with SVDV. These results should encourage further work towards the development of a DNA vaccine against SVDV.
INTRODUCTIONSwine vesicular disease (SVD) is a highly contagious viral pig disease, characterized by the appearance of vesicles on the coronary bands, heels of the feet and less commonly on the snout and tongue. Due to the similarity of these lesions to those caused by foot-and mouth-disease (FMD), SVD is subject to international controls and is listed by the World Organization for Animal Health. SVD was first identified in Italy in 1966(Nardelli et al., 1968 and several more outbreaks have been reported subsequently in Europe and eastern Asia (Brocchi et al., 1997). However, in the recent past, reports of SVD have been limited to Portugal and Italy.SVD vaccines have been developed previously to control the disease, both in monovalent form (Gourreau et al., 1975) and in combination with FMD (Mitev et al., 1978), and an SVD subunit vaccine has also been described, although it was not very efficacious (Jiménez-Clavero et al., 1998). Although the inactivated virus vaccines are effective in protecting against clinical signs, there has been little, if any, assessment made of their ability to reduce wild-type virus transmission and no effective vaccine is available commercially. Once introduced, SVD could be a difficult disease to eradicate and improved methods of control would be highly beneficial, including the development of safer and more effective vaccines to protect and control this disease.Suicidal DNA vaccines, based on the alphavirus replicon, have emerged as an important strategy to enhance immunogenicity and to improve the biosafety of conventional DNA vaccines (Berglund et al., 1998;Leitner et al., 1999;Lundstrom, 2000). Unlike the conventional DNA vaccine construct in which heterologous gene expression is driven directly by the RNA polymerase II-dependent promoter, suicidal DNA vaccines based on the replicon of alphaviruses, including Sindbis viru...