#11-005

Complete

Date Full Report Received

06/14/2012

Date Abstract Report Received

06/14/2012

Investigation

Institution: , ,
Primary Investigator:

FMD is the one of the most feared viral disease that can affect livestock, including swine. Although this disease appeared to be eliminated from most developed nations by the end of last century, recent outbreaks in Europe, Japan, Taiwan, South Korea, Eastern Russia, etc, have demonstrated that infection can spread as wild fire affecting any nation and causing devastating economic and social consequences. Furthermore, post 9/11 the US is threatened by the potential deliberate release of FMDV by terrorist groups. Therefore, it is essential to develop new control strategies that could confer very early protection and stop disease spread. It has been demonstrated for other viral diseases that live-attenuated vaccines are one of the best choices to obtain a strong early and long-lasting protection. The current FMD vaccine is a formulation of inactivated WT virus antigen prepared in high containment bio-security level 3 facilities. This vaccine requires 7 days to induce protection, a time during which vaccinated animals are still susceptible to one of the fastest replicating viruses in nature. In addition the vaccine is prepared from highly virulent circulating virus strains that despite extreme caution and care in the manufacturing process, could result in outbreaks by accidental virus release as it happened in the United Kingdom in 2007 (estimated cost $2B). Our goal is to develop alternative control strategies that could improve current FMD countermeasure programs. An attenuated vaccine is expected to elicit more rapid innate immunity and a long lived adaptive immunity to effectively control disease. Moreover, induction of innate immunity could result in early protection against multiple FMDV serotypes. From the production perspective, use of an attenuated FMDV strain will reduce the consequences of accidental outbreaks caused by accidental release of virus from vaccine manufacturing facilities. Importantly, attenuated strains are excellent new tools to study the interactions between FMDV and the host immune system and ultimately could lead to the development of novel strategies to counteract FMD. During the past year and with the support of NPB we have successfully derived a mutant strain of FMDV that did not cause disease in swine (FMDV-SAP mutant). Interestingly inoculation of swine with this mutant strain induced a strong immune response that protected animals against infection with the parental (wild type) virus, as early as two days post vaccination. Studies in animals and in cultured swine cells demonstrated that, in contrast to the parental wild type virus, the mutant variant was unable to block some inflammatory responses thus limiting dissemination of the virus beyond the original site of inoculation. Furthermore  we have started studies to add more mutations to this virus aiming to increase the stability of the original mutations therefore decreasing the probability of reversion to virulence. Our results indicated that manipulation of the viral genome in the region that encodes for the leader protein is a viable alternative to derive less pathogenic FMDV strains that could be used as the basis for live attenuated vaccines against FMD or as seeds to grow the virus for manufacturing safer inactivated vaccines. Although this strategy is far from being used in countries that are FMD free without vaccination, it could be an affordable alternative to control FMD in regions of the world where the disease is enzootic thereby decreasing the risks of dissemination to disease-free nations. Ultimately a combination of strategies tailored to each region of the world will eventually succeed to eradicate this feared disease.
(Teresa de los Santos PhD, PIADC, ARS, USDA. TEL: (631) 323-3020. E-mail: teresa.delossantos@ars.usda.gov).