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Title: Use of replication-defective adenoviruses to develop vaccines and biotherapeutics against foot-and-mouth disease

item Grubman, Marvin
item Diaz San Segundo, Fayna
item DIAS, CAMILA - Oak Ridge Institute For Science And Education (ORISE)
item MORAES, MAURO - University Of Connecticut
item PEREZ-MARTIN, EVA - Oak Ridge Institute For Science And Education (ORISE)
item De Los Santos, Teresa

Submitted to: Future Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/14/2012
Publication Date: 8/15/2012
Citation: Grubman, M.J., Diaz San Segundo, F.C., Dias, C.C., Moraes, M.P., Perez-Martin, E., De Los Santos, T.B. 2012. Use of replication-defective adenoviruses to develop vaccines and biotherapeutics against foot-and-mouth disease. Future Virology. 7(8):767-778.

Interpretive Summary: Foot-and-mouth disease virus (FMDV) is an antigenically variable virus that causes an economically devastating disease of cloven-hoofed animals. Vaccines produced by chemical inactivation of virus are available, but there are concerns about their safety and about the ability to serologically distinguish vaccinated animals from infected animals. We initiated a project which uses a replication-defective human adenovirus to deliver an FMD subunit vaccine (Ad5-FMD). Production of this vaccine does not require expensive high-containment manufacturing facilities, can be made in the U.S., which currently prohibits work with infectious FMDV on the mainland, and allows distinction of infected from vaccinated animals. This Ad5-FMD vaccine can protect both swine and bovines after one inoculation. In collaboration with the Department of Homeland Security and the biotechnology company GenVec, Inc. this vaccine format is currently under regulatory licensure approval for inclusion in the U.S. Veterinary Vaccine Stockpile. More recently we have developed second generation Ad5-FMD vaccines that when delivered subcutaneously have enhanced efficacy as compared to our first generation vaccine inoculated intramuscularly. In addition, since FMDV replicates and spreads very rapidly we have developed a biotherapeutic approach to induce protection prior to the vaccine induced adaptive immunity. We constructed Ad5 vectors containing the genes for porcine and bovine interferons (IFN). Inoculation of swine with Ad5 vectors containing IFN induces protection in 1 day. We obtained similar results in cattle. We propose that a combination of Ad5-IFN and Ad5-FMD can induce both rapid and long-lasting protection.

Technical Abstract: We have developed a replication-defective human adenovirus (Ad5) vectored foot-and-mouth disease (FMD) vaccine platform that with one inoculation protects both swine and cattle from subsequent challenge with homologous virus. This Ad5-FMD vaccine delivery system has undergone testing following the requirements of the Center for Veterinary Biologics of the Animal Plant and Health Inspection Service, U.S. Department of Agriculture needed for subsequent inclusion in the U.S. National Veterinary Vaccine Stockpile. We will describe the approaches we have taken to improve the potency and efficacy of this vaccine platform. Furthermore, we will describe the development of biotherapeutics to induce rapid protection against FMD virus prior to vaccine induced immunity and the use of a combination of these approaches to stimulate both rapid and long-lasting immunity.