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Combined Vaccine-Drug or -Cytokine Therapy Strategy May Be Needed 

Because the foot-and-mouth disease (FMD) virus binds preferentially to the anb6 integrin receptor, which is distinct from other RGD-binding integrins, it may be possible to develop agents that specifically block this binding, according to Andrew King, head of molecular biology at the Pirbright Laboratory in Surrey, England. Although Pirbright scientists are not developing antiviral agents, combined drug and vaccine treatments may be needed for FMD because “persistence is the major problem that has to be solved before it's possible to vaccinate completely safely,” he says. 

Research on the leader (L) proteinase of the FMD virus could point the way to drug targets. For example, attempts by U.S. Department of Agriculture researchers at the Plum Island Animal Disease Center to develop an attenuated virus vaccine by knocking out the L proteinase coding region of the virus led to new insights into the role of this enzyme during infection. The first FMD viral protein to be translated, the L proteinase not only processes other FMD proteins, but also helps in shutting down host cell protein production by cleaving a host initiation factor. 

In doing so, it also suppresses host interferon production, enabling the virus to spread unchecked until the adaptive immune response kicks in. Recently, Marvin Grubman of the FMD research unit of Plum Island and his colleagues determined that interferon-alpha (INF-a) and INF-b are equally effective in blocking replication of the FMD virus. Because this suppression occurs at the translation level and seems to involve the viral L proteinase, the host double-stranded RNA-dependent protein kinase, or PKR, may play a role in inhibiting virus replication.

Although a few new vaccine and antiviral candidates are moving along in development, scientists involved in FMD research concede several years of testing will be required before any of these projects come near commercial development. Meanwhile, the viruses continue to flare up around the globe, giving a rude awakening even to countries that had been free of FMD for more than 70-plus years, such as Japan, which experienced an outbreak last year. The chances of an outbreak occurring in the United States are “quite great”given the amount of travel between North America and Europe, according to David Huxsoll, director of the Plum Island labs.