e Classical swine fever, caused by classical swine fever virus (CSFV), is a highly contagious disease that results in enormous economic losses in pig industries. The E2 protein is one of the main structural proteins of CSFV and is capable of inducing CSFVneutralizing antibodies and cytotoxic T lymphocyte (CTL) activities in vivo. Thymosin ␣-1 (T␣1), an immune-modifier peptide, plays a very important role in the cellular immune response. In this study, genetically engineered Lactobacillus plantarum bacteria expressing CSFV E2 protein alone (L. plantarum/pYG-E2) and in combination with T␣1 (L. plantarum/pYG-E2-T␣1) were developed, and the immunogenicity of each as an oral vaccine to induce protective immunity against CSFV in pigs was evaluated. The results showed that recombinant L. plantarum/pYG-E2 and L. plantarum/pYG-E2-T␣1 were both able to effectively induce protective immune responses in pigs against CSFV infection by eliciting immunoglobulin A (IgA)-based mucosal, immunoglobulin G (IgG)-based humoral, and CTL-based cellular immune responses via oral vaccination. Significant differences (P < 0.05) in the levels of immune responses were observed between L. plantarum/pYG-E2-T␣1 and L. plantarum/pYG-E2, suggesting a better immunogenicity of L. plantarum/pYG-E2-T␣1 as a result of the T␣1 molecular adjuvant that can enhance immune responsiveness and augment specific lymphocyte functions. Our data suggest that the recombinant Lactobacillus microecological agent expressing CSFV E2 protein combined with T␣1 as an adjuvant provides a promising strategy for vaccine development against CSFV. C lassical swine fever virus (CSFV), a member of the Pestivirus genus of the Flaviviridae family, is a small, enveloped, singlestranded RNA virus. The genome of CSFV consists of a positivestranded RNA molecule of about 12.3 kb, encoding a single open reading frame that is translated into a 3,898-amino-acid polyprotein, giving rise to different CSFV proteins after coprocessing and after translational processing (1, 2). Of these, the E2 structural protein encompasses major antigenic domains and cytotoxic T lymphocyte (CTL) epitopes, suggesting a promising candidate for an immunogen with the capacity to induce neutralizing antibodies and CTL activities against CSFV (3-10). CSFV often causes severe and lethal disease in pigs, resulting in enormous economic losses in pig industries (11,12). Therefore, the development of effective vaccines against CSFV infection is an issue of growing importance.For the development of CSFV vaccines, the roles of neutralizing antibody-based humoral immune responses (13, 14) and CTL-based cellular immune responses (15-20) have been both highlighted. Furthermore, the invasion of CSFV often initiates at mucosal surfaces, particularly intestinal tissues, and thus, vaccination inducing IgA-based protective mucosal immunity via the mucosal approach could effectively prevent the virus from entering the body via mucosa and its further spread to the systemic circulation. Taken together, the design of new vaccines ...