Submitted to: Virus Research
Publication Type: Peer reviewed journal
Publication Acceptance Date: 1/13/2012
Publication Date: 1/21/2012
Citation: Yang, Z., Wu, R., Li, L., Xiong, Z., Zhao, H., Li, R.W., Guo, D., Pan, Z. 2012. Chimeric classical swine fever (CSF)-Japanese encephalitis (JE) viral particles as a non-transmissible bivalent marker vaccine candidate against CSF and JE infections. Virus Research. 165(1):61-70. Interpretive Summary: Viral infections have a significant economic impact on the livestock industry especially since they can spread rapidly within a herd. Classical swine fever virus (CSFV) is the pathogen that causes a severe disease with symptoms of fever, internal bleeding, and low white blood cell counts. In addition to its high mortality rate, CSFV also increases the risk of other pathogens simultaneously causing infection. In this study, we developed a new, non-infectious virus that contained a specific sequence of DNA from the Japanese encephalitis virus’s (JEV) E protein. We analyzed the growth characteristics of this new virus and evaluated its potential as an effective vaccine against CSFV and JEV infections in animals. Our results show that vaccination with this new virus created immunity against infection by either preventing infection or by accelerating the ability of the body to remove the infection. Immunization of this virus with other vaccines or vaccine-enhancing molecules may result in a better delivery of the vaccine and an increase in protective immunity. This unique vaccination strategy may have a broad implication in the design of new vaccines against infections, such as parasitic and viral infections, in livestock.
Technical Abstract: A trans-complemented CSF- JE chimeric viral replicon was constructed using an infectious cDNA clone of the CSF virus (CSFV) Alfort/187 strain. The E2 gene of CSFV Alfort/187 strain was deleted and the resultant plasmid pA187delE2 was inserted by a fragment containing the region coding for a truncated envelope protein ('E, the domain III) of JE virus (JEV) to generate the recombinant cDNA clone, pA187delE2/JEV-'E. Porcine kidney 15 (PK15) cells that constitutively express the CSFV E2p7 proteins were then transfected with in vitro-transcribed RNA from pA187delE2/JEV-'E. As a result, chimeric CSF-JE virus replicon particles (VRPs), rv187delE2/JEV-'E, were rescued. In a mouse model, immunization using the chimeric CSF-JE VRPs induced a strong production of JEV-specific IgG and conferred protection against a lethal JEV challenge. Pigs immunized with the chimeric CSF-JE VRPs displayed strong anti-CSFV and anti-JEV humoral immune responses and protection against CSFV and JEV challenge infections. Compared to a commercial inactivated JEV vaccine, the chimeric VRPs seemingly induced a more rapid IgG response and led to a stronger production of JEV neutralizing antibodies. Our evidence suggests that E2-complemented chimeric CSF-JE VRPs not only have the potential as a live-attenuated non-transmissible vaccine candidate against CSF and JE but also serve as a potential marker vaccine for CSF in pigs. Together, our data suggest that the non-transmissible chimeric VRPs expressing foreign antigenic proteins may represent a promising strategy for bivalent marker vaccine design.