Caister Academic Press

Control of Foot-and-mouth Disease by Using Replication-defective Human Adenoviruses to Deliver Vaccines and Biotherapeutics

Fayna Diaz-San Segundo, Gisselle Medina, Marvin J. Grubman and Teresa de los Santos
from: Foot-and-Mouth Disease Virus: Current Research and Emerging Trends (Edited by: Francisco Sobrino and Esteban Domingo). Caister Academic Press, U.K. (2017) Pages: 333-356.


Foot-and-mouth disease (FMD) is one of the most important viral-diseases that can affect livestock worldwide. Although the disease has been successfully controlled in many geographic regions, mainly due to the enforcement of surveillance and trading policies and the use of an available inactivated whole virus vaccine formulation, challenges remain as outbreaks are constantly detected in most of the developing world. With the expansion of globalization and the exponential growth of population in today's world, recent outbreaks have wreaked havoc in disease-free countries resulting in devastating economic consequences. Novel vaccination policies that could be massively produced anywhere, that could induce early protection after vaccination at a low risk and affordable cost are needed. A novel vaccine approach using a recombinant replication-defective human adenovirus type 5 (Ad5) vector has recently been developed and has been granted for the first time in the last 50 years, a provisional U.S. license for production and use in the U.S mainland in outbreak situations. The Ad5-FMD vaccine delivers only FMDV capsid and some non-structural (NS) viral coding regions required for capsid processing and improved expression. Animals vaccinated with Ad5-FMD can be readily differentiated from infected animals (DIVA) using diagnostic assays employing the NS proteins not present in the vaccine and production of this vaccine does not require expensive high-containment manufacturing facilities since it does not contain infectious FMDV. One inoculation of this Ad5-FMD subunit vaccine can induce rapid, within 7 days, and relatively long-lasting protection in swine. Similarly cattle inoculated with one dose of this recombinant vector are rapidly protected from direct and contact exposure to virulent virus. Furthermore, cattle given two doses of this vaccine developed high levels of FMDV-specific neutralizing antibodies, suggesting that the Ad5 vector approach may be useful in semiannual FMD vaccine campaigns. To stimulate protection prior to the vaccine-induced adaptive immune response we have explored the possibility of using biotherapeutics also delivered by recombinant Ad5. Delivery of type I, type II and type III interferon (IFN) can fully protect swine against challenge with multiple FMDV serotypes. Similarly, delivery of type III IFN can protect cattle against FMD. Interestingly a combined approach of Ad5-FMD vaccine and Ad5-IFN can protect animals as early as 1 day post vaccination and protection can be complete. Thus, this combination approach successfully addresses a number of concerns of FMD-free countries with the current disease control plan. By rapidly limiting virus replication and spread, this strategy may reduce the number of animals that need to be slaughtered during an outbreak as well as allow for differentiation of vaccinated from infected animals In this chapter we will review the development of these approaches and current efforts to improve the strategy to make it affordable and effective for global use read more ...
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