Novel Foot-and-Mouth Disease Vaccine Platform: Formulations for Safe and DIVA-Compatible FMD Vaccines With Improved Potency

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, 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 non-structural antigens, there is still a risk that small amounts of non-structural proteins may 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 conserved non-structural proteins 3D(pol) 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 inactivated FMD-LL3B3D-A(24) Cruzeiro vaccine in cattle against wild-type challenge with A(24) Cruzerio. A proprietary adjuvant system was used to formulate the vaccines that conferred effective protection at low doses while maintaining the DIVA compatibility. In contrast to wild-type FMDV, the recombinant FMD-LL3B3D mutant viruses have been shown to induce no clinical signs of FMD and no shedding of virus in cattle or pigs when inoculated as a live virus. 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 initiatives.