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Title: Inactivated and subunit vaccines against porcine reproductive and respiratory syndrome: 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: Review Article
Publication Acceptance Date: 4/30/2015
Publication Date: 6/1/2015
Citation: Renukaradhya, G.J., Meng, X.J., Calvert, J.G., Roof, M., Lager, K.M. 2015. Inactivated and subunit vaccines against porcine reproductive and respiratory syndrome: Current status and future direction. Vaccine. 33(27):3065-3072.

Interpretive Summary: Porcine reproductive and respiratory syndrome (PRRS) is a swine disease that was first recognized in 1987 in the United States. Within a few years it had spread globally to become the primary disease concern for pork producers. The cause, PRRS virus, was discovered in 1992 and within 2 years modified-live and killed PRRS virus vaccines were developed. Modified-live vaccines contain a wild-type virus that has been mutated to attenuate the disease causing capacity of the virus. It still replicates in the pig and can stimulate an immune response, but does not induce disease. Killed virus vaccines contain wild-type virus that has been inactivated so it will not replicate in the pig, but still induce an immune response. Although these vaccines have been widely used, they still have limitations because they do not provide complete protection against emerging field strains of the virus. Moreover, there are safety concerns due to the potential for the modified-live vaccine to revert to its wild-type form. Although there are minimal safety concerns for the killed virus vaccines, they have not provided as much protection as modified-live vaccines. There is a critical need to develop improved PRRS virus vaccines that have better cross-protection as well as increased safety. This review summarizes information on different strategies to develop PRRS virus vaccines that do not replicate in swine, how such vaccines should be safer, and how they may play a role in future attempts to not only eliminate PRRS virus from a herd, but from a region.

Technical Abstract: Within a few years of its emergence in the late 1980's, the PRRS virus had spread globally to become the foremost infectious disease concern for the pork industry. Since 1994, modified live-attenuated vaccines against porcine reproductive and respiratory syndrome virus (PRRSV-MLV) have been widely used, but have failed to provide complete protection against emerging and heterologous field strains of the virus. Moreover, like many other MLVs, PRRSV-MLVs have safety concerns including vertical and horizontal transmission of the vaccine virus and several documented incidences of reversion to virulence. Thus, the development of efficacious inactivated vaccines is warranted for the control and eradication of PRRS. Since the early 1990's, researchers have been attempting to develop inactivated PRRSV vaccines, but most of the candidates have failed to elicit protective immunity even against homologous virus challenge. Recent research findings relating to both inactivated and subunit candidate PRRSV vaccines have shown promise, but they need to be pursued further to improve their heterologous efficacy and cost-effectiveness before considering commercialization. In this comprehensive review, we provide information on attempts to develop PRRSV inactivated and subunit vaccines. These includes various virus inactivation strategies, adjuvants, nanoparticle-based vaccine delivery systems, DNA vaccines, and recombinant subunit vaccines produced using baculovirus, plant, and replication-deficient viruses as vector vaccines. Finally, future directions for the development of innovative non-infectious PRRSV vaccines are suggested. Undoubtedly there remains a need for novel PRRSV vaccine strategies targeted to deliver cross-protective, non-infectious vaccines for the control and eradication of PRRS.