Submitted to: Future Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/1/2009
Publication Date: 1/1/2010
Publication URL: http://hdl.handle.net/10113/44511
Citation: Grubman, M.J., Moraes, M.P., Neilan, J., Ettyreddy, D., Butman, B.T., Brough, D.E., Brake, D.A. 2010. Adenovirus serotype 5 vectored foot-and-mouth disease subunit vaccines: the first decade. Future Virology. 5(1):51-64. Interpretive Summary: Foot-and-mouth disease virus (FMDV) is an antigenically variable virus consisting of 7 serotypes and multiple subtypes and 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. A possible alternative approach to develop safe, effective FMD vaccines is to produce viral subunit vaccines which do not contain infectious FMDV and lack the genetic information for a number of viral nonstructural proteins. Approximately 10 years ago we initiated a project which used a replication-defective human adenovirus to deliver this vaccine (Ad5-FMDV). Thus, 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 animals inoculated with this marker vaccine can readily be differentiated from infected animals using diagnostic assays employing the viral nonstructural proteins not present in the vaccine. We have demonstrated that 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. we have expanded these studies in cattle and demonstrated its effectiveness in both direct inoculation challenge studies as well as contact challenge studies. Furthermore, we have developed manufacturing protocols to allow scalable production of these FMD molecular vaccine products, regulatory licensure approval, and inclusion in the U.S. Veterinary Vaccine Stockpile. We have also constructed and initiated cattle efficacy testing of Ad5 vectors containing the capsid coding regions from other FMDV serotypes and subtypes.
Technical Abstract: Here we present the results of the first decade of development of a replication-defective human adenovirus (Ad5) containing the capsid and 3C protease coding regions of foot-and-mouth disease virus (FMDV) as a vaccine candidate. In proof-of concept studies we demonstrated that a single inoculation with this vaccine vector containing the capsid of FMDV A24 Cruzeiro protected both swine and cattle following homologous challenged by direct inoculation one week post-vaccination. We have expanded these studies in cattle with larger numbers of animals and by testing the vaccine in direct contact challenge studies, including the ability to prevent FMDV shed and transmission. Furthermore, we have developed manufacturing protocols to allow scalable production of these FMD molecular vaccine products for USDA licensure approval, and inclusion in the U.S. Veterinary Vaccine Stockpile. We have constructed and initiated cattle efficacy testing of Ad5 vectors containing the capsid coding regions from other FMDV serotypes and subtypes as well as initiated studies to improved FMD molecular vaccine potency.