Construction and Evaluation of an Efficient Live Attenuated Choleraesuis Vaccine and Its Ability as a Vaccine Carrier to Deliver Heterologous Antigens.

The gram-negative facultative intracellular pathogen serotype Choleraesuis, also known as . Choleraesuis, is a major financial loss for the pig business. C500 is a vaccine strain that has been used for preventing . Choleraesuis infection in pigs for many years in China. Although it possessed good immunogenicity and protection efficacy, it still showed severe side effects. The truncation of the key gene in C500 was believed to take the major responsibility for its attenuation. To achieve a good balance between attenuation and immunogenicity, was restored to an active state, and other essential virulent genes of , , , and were evaluated for their effects of deletion on safety and immunogenicity. Animal experiments demonstrated that C5001 (C500 Δ) and C5002 (C500 Δ) showed an excellent ability to induce an immune response. To further decrease the endotoxic activity, the combination mutations of Δ Δ::P Δ were introduced into the mutant strains to generate 1'-dephosphorylated lipid A. Animal experiments showed that SC3 (C500 Δ Δ Δ:: P Δ) induced higher levels of IgG and secreted IgA antibodies and provided a higher protection rate than SC1 (C500 Δ Δ:: P Δ) and SC2 (C500 Δ Δ Δ:: P Δ). We also evaluated the ability of SC3 (C500 r Δ Δ Δ:: P Δ) as a vaccine carrier to deliver heterologous protein antigens and polysaccharide antigens. The results indicated that SC3 (C500 r Δ Δ Δ:: P Δ) showed an excellent ability to deliver heterologous antigens and induce the host to produce high levels of antibodies. Together, these results indicate that we constructed a safe and efficient attenuated strain of the . Choleraesuis vaccine, which demonstrated strong resistance to infection with wild-type . Choleraesuis and can be employed as a universal vector for the delivery of recombinant antigens.