Location: Location not imported yet.Title: Novel Foot-and-Mouth Disease vaccine platform:Formulations for safe and DIVA-compatible FMD vaccines with improved potency
|HARDHAM, JOHN - Zoetis
|KRUG, PETER - Former ARS Employee
|PACHECO, JUAN - Former ARS Employee
|THOMPSON, JAMES - Zoetis
|DOMANOWSKI, PAUL - Zoetis
|Rieder, Aida - Elizabeth
Submitted to: Frontiers in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/13/2020
Publication Date: 9/25/2020
Citation: Hardham, J., Krug, P., Pacheco, J., Thompson, J., Domanowski, P., Gay, C.G., Rodriguez, L.L., Rieder, A.E. 2020. Novel Foot-and-Mouth disease vaccine platform: Formulations for safe and DIVA-compatible FMD vaccines with improved potency. Frontiers in Veterinary Science. https://doi.org/https://doi.org/10.3389/fvets.2020.554305.
Interpretive Summary: Foot and mouth disease (FMD) is a devastating and highly contagious viral disease of livestock and posting a risk to FMD-free countries. Current FMDV vaccines are made by growing large amounts of virus in cell culture, inactivating it using chemicals, concentrating the virus and formulated using appropriate dilutions buffers and adjuvants to improve the immunity. Currently, vaccine manufacturing involves the use of infectious virus and virus escapes from production facilities have caused outbreaks in FMD-free countries. This is one reason that US regulations do not allow vaccine production using live FMD virus. A novel vaccine platform, was discovered by ARS scientists using genetic engineering to remove one of the viral proteins (called leader) that is critical for causing disease and transmission in infected animals. Additionally, researchers introduced genetic markers that allow to differentiate infected from vaccinated animals, a feature critical during disease eradication efforts. This novel virus is an ideal platform for safe vaccine production since the virus, while still capable of growing in cell culture, does not cause disease in animals. The present study showed that this novel vaccine formulated with a company proprietary adjuvant is capable to protect cattle from exposure to FMD virus. These results allow further development of this promising technology aimed at achieving US domestic FMD vaccine production.
Technical Abstract: Inactivated, wild-type foot-and-mouth disease virus (FMDV) vaccines are currently used to control FMD around the world. These traditional FMD vaccines are produced using large quantities of infectious, virulent, wild-type FMD viruses are, with the associated risk of virus escape from manufacturing facilities or incomplete inactivation during the vaccine formulation process. While higher quality vaccines produced from wild-type FMDV are processed to reduce nonstructural antigens, they are not fully DIVA compatible since small amounts of nonstructural proteins may still be present in the final product. A novel, antigenically marked FMD-LL3B3D vaccine platform under development by Zoetis, Inc. and the USDA-ARS, consists of a highly attenuated virus platform containing negative antigenic markers in the non-structural proteins 3Dpol and 3B that render resultant vaccines fully DIVA compatible. This vaccine platform allows for the easy exchange of capsid coding sequences to create serotype-specific vaccines. Here we demonstrate the efficacy of the FMD-LL3B3D-A24 Cruzeiro vaccine in cattle against wild-type challenge with A24 Cruzerio. A proprietary adjuvant system is used to formulate the vaccines that increases the potency of the final product while maintaining the DIVA compatibility. In contrast to wild-type FMDV, the recombinant FMD-LL3B3D mutant viruses induced no clinical signs of FMD and no shedding of virulent virus in cattle or pigs when inoculated as a live virus as part of the safety test for the platform. The FMD-LL3B3D vaccine platform, currently undergoing development in the US, provides opportunities for safer vaccine production with full DIVA compatibility in support of global FMDV control and eradication.