Studies On The Epitope Vaccine Against Classical Swine Fever Virus

Classical swine fever (CSF) is a swine disease having devastating impact on the livestock industry, and the outbreaks of the classical swine fever usually cause great economic losses. Therefore, the surveillance, prophylaxis and control of the CSF outbreaks are treated seriously all over the world. Classical swine fever virus (CSFV) is the etiological agent of classical swine fever. In the 1950s'the"54-III"live attenuated vaccine (the C strain) was successfully developed in China by adaptation of a highly virulent strain of classical swine fever virus to the rabbits, and the immunoprophylaxis strategy using this vaccine has been proved to make great contributions to the control of the CSF epidemics in China. The safety and efficacy of this vaccine have been widely recognized throughout the world. However, the failures in immunization with this vaccine and the sporadic CSF epidemics have been seen on the rise in the recent years. Besides, the vaccinated pigs could hardly be differentiated from those infected by the field strains serologically. All these mentioned above are now severely affected the livestock industry development and the international trading of pigs and pork products. Hence, we aim to develop a new CSFV vaccine– the CSFV epitope marker vaccine based on our epitope-vaccine strategy.In this study, a series of recombinant immunogens targeted on TAVSPTTLR, the well-known conserved linear neutralizing epitope on the glycoprotein E2 of classical swine fever virus, were prepared. Systemic research was performed on the basis of these immunogens. The antigenicity and immunogenicity of these immunogens were analyzed, identifying several immunogens which satisfied the basic requirement of a vaccine candidate. The challenge/protection test was performed on the rabbit model of the live attenuated vaccine to evaluate their potential as vaccine candidates, discovering that the immunogen, which contain 6 copies of the epitope in a single molecule, could provide the susceptible animals protection against virus challenge. We further demonstrated through the in vitro neutralization test that the vaccine candidate managed to induce antiviral humoral immunity. These results demonstrated that the vaccine candidate was able to protect the susceptible animals from CSFV infection. In this work, we discovered: (1) the natural microenvironment of the epitope contributed essential structural information for the induction of the epitope-specific neutralizing antibodies; (2) the immunogens focused on TAVSPTTLR managed to induce neutralizing antibodies and provide protection, compensating the contribution rendered by the epitope context.The work on the TAVSPTTLR epitope made a better understanding of this conserved linear neutralizing epitope on the CSFV E2 glycoprotein, which provided a solid foundation for the further development of the marker CSFV epitope vaccines. Besides, the work was proof-of-concept, demonstrating the epitope vaccine strategy based on the conserved linear neutralizing epitope stood sound not only in theory but also in practice.