#06-177

Complete

Date Full Report Received

06/24/2008

Date Abstract Report Received

06/24/2008

Investigation

Institution:
Primary Investigator:
Co-Investigators: Asit Pattnaik

This project is based on two main premises: 1) the conviction that the use of vaccines will always be a cost-efficient method and the preferred approach to control PRRSV infections, and 2) the notion that the best type of vaccine against PRRSV has proved to be the modified live, attenuated vaccines. In all likelihood, the live vaccines are most effective because their components that are determinants of protection ( a.k.a. as antigens or immunogenic epitopes) are “seen” by the pig’s immune system in a similar way as are seen those of live wild-type (fully infectious) PRRSV. A nationwide colloquium held by PRRSV experts in June 2007 at the University of Illinois (Urbana-Champaign) reached the conclusion that a new vaccine for PRRSV may require up to 10 years to reach the market, and that several technical approaches may be followed to develop such novel vaccine. However, the expert group concluded that the live, replicating type of vaccine seems generally to be the most favored, based on the robust immunity that can be developed in the animal after the application of this type of vaccine. Our ultimate goal is to develop a live vaccine of safety and efficacy that would be compatible with the ability of cleansing the PRRSV infection, that is, compatible with the ability of differentiating, through a simple test, the vaccinated/protected animals from those that have suffered infection by wild-type PRRSV. Our technical approach to the improvement of PRRS live vaccines is based on the notion that mapping the genes causing virulence in PRRSV should provide information for the development of a differential PRRSV vaccine of unprecedented safety and efficacy. The capacity of PRRSV to cause serious pathologic changes is called virulence. In our system we measure viral virulence in relation to the virus’ ability of producing abortion in pregnant sows. This virulence is caused by the different genes and its proteins composing the PRRSV. The main expected outcome of this research is the alteration of the genes of the PRRS viruses to develop live attenuated/marker vaccine strains. The research we report herein uses chimeras, which are strains obtained by the mixing of genes of two heterologous PRRSV strains of different level of virulence. Engineering of new live-attenuated PRRSV marker vaccines requires knowledge of the genetic make-up of PRRS virulence and identifying small areas of the proteins which can be eliminated from the vaccine without affecting the virus’ ability to multiply in the pig. This concept is similar to that applied for Pseudorabies marker vaccines. The differential vaccines, which, like in the example of Pseudorabies, were originally called “marker vaccines” are now also identified as DIVA vaccines (which stands for “Differentiating Infected from Vaccinated Animals”). This year, through the support from NPB #: 06-177, we are able to report the development of the first DIVA live vaccine for PRRSV through the elimination of small protein fragment (epitope) that, although falling short of being a perfect marker, serves as proof of the concept and encourages further research on more efficient small protein fragments that can be used as markers. Likewise we report that PRRSV virulence, while evidently is under control of more than one, perhaps several, genes, can be irreversibly modulated by changes in just a few important PRRSV genes, one of which is GP5. This knowledge and the realization that the virulence studies can be continued through the use of a recently identified homologous pair ( virulent wt and vaccine strain pair), without using chimeras, will significantly speed the characterization of the minimal number of segments of PRRSV genes that need to be altered to obtain a safe (non-virulent ) efficacious vaccine candidate.