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Title: Live porcine reproductive and respiratory syndrome virus vaccines: current status and future direction

item RENUKARADHYA, GOURAPURA - The Ohio State University
item MENG, XIANG-JIN - Virginia Polytechnic Institution & State University
item CALVERT, JAY - Zoetis
item ROOF, MICHAEL - Boehringer Ingelheim
item Lager, Kelly

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/23/2015
Publication Date: 8/7/2015
Citation: Renukaradhya, G.J., Meng, X., Calvert, J.G., Roof, M., Lager, K.M. 2015. Live porcine reproductive and respiratory syndrome virus vaccines: current status and future direction. Vaccine. 33(33):4069-4080.

Interpretive Summary: Porcine reproductive and respiratory syndrome (PRRS) is the number one health concern for US pork producers with current annual economic losses in North America estimated at one billion US dollars. The disease is caused by PRRS virus which was discovered in 1991. The first modified-live PRRSV vaccine (PRRSV-MLV) became commercially available in late 1994. Field and experimental trials demonstrated this vaccine provided good protection against viruses closely related to the vaccine virus, however, the vaccine did not protect as well against more distantly related field isolates. Although there have been many advances in understanding the biology and ecology of PRRSV; there is still a significant knowledge gap in how the virus causes disease, and why it is difficult to produce better PRRSV vaccines. This review provides insights on past and current research efforts focusing on improving available vaccines that use attenuated infectious PRRSV as well as experimental vaccines that have been developed using novel technologies.

Technical Abstract: Porcine reproductive and respiratory syndrome (PRRS) caused by PRRS virus (PRRSV) was reported in the late 1980's. PRRS still is a huge economic concern to the global pig industry with a current annual loss estimated at one billion US dollars in North America alone. It has been 20 years since the first modified live-attenuated PRRSV vaccine (PRRSV-MLV) became commercially available. PRRSV-MLVs provide homologous protection and help in reducing shedding of heterologous viruses, but they do not completely protect pigs against heterologous field strains. There have been many advances in understanding the biology and ecology of PRRSV; however, the complexities of virus-host interaction and PRRSV vaccinology are not yet completely understood leaving a significant gap for improving breadth of immunity against diverse PRRS isolates. This review provides insights on immunization efforts using infectious PRRSV-based vaccines since the 1990's, beginning with live PRRSV immunization, development and commercialization of PRRSV-MLV, and strategies to overcome the deficiencies of PRRSV-MLV through use of replicating viral vectors expressing multiple PRRSV membrane proteins. Finally, powerful reverse genetics systems (infectious cDNA clones) generated from more than 20 PRRSV isolates of both genotypes 1 and 2 viruses have provided a great resource for exploring many innovative strategies to improve the safety and cross-protective efficacy of live PRRSV vaccines. Examples include vaccines with diminished ability to down-regulate the immune system, positive and negative marker vaccines, multivalent vaccines incorporating antigens from other porcine pathogens, vaccines that carry their own cytokine adjuvants, and chimeric vaccine viruses with the potential for broad cross-protection against heterologous strains. To combat this devastating pig disease in the future, evaluation and commercialization of such improved live PRRSV vaccines is a shared goal among PRRSV researchers, pork producers and biologics companies.