Location: Foreign Animal Disease Research
Project Number: 8064-32000-057-64-S
Project Type: Specific Cooperative Agreement
Start Date: Jan 31, 2014
End Date: Feb 1, 2017
Foot-and-mouth disease (FMDV) is an antigenically variable virus. Vaccination requires the production of inactivated virus antigen against all serotypes and multiple subtypes within each serotype. Current FMD vaccines are administered parenterally but since FMDV infects animals via the respiratory tract, this route may not block virus replication, but only clinical disease. Specific objectives include: 1. Evaluate adjuvants that could be used in combination with FMD vaccines to enhance mucosal as well as generalized immune responses. 2. Evaluate alternative routes of inoculation to improve potency and efficacy of Ad5-FMD. 3. Broaden the immune response of Ad5-FMD vaccines so that one vaccine could protect animals against multiple strains of FMDV and potentially against multiple FMDV serotypes.
To improve the potency and efficacy of current Ad5-FMD vaccine candidates, we will examine the use of alternative routes of inoculation and novel adjuvants. We will study the efficacy of Ad5-FMD vaccines alone or in combination with adjuvants such as toll like receptor agonists or mucosal specific enterotoxin adjuvants administered parenterally by subcutaneous inoculation or transdermal administration using a needle free device. Since FMDV is an antigenically variable virus and consists of 7 serotypes and multiple subtypes, protection against this disease requires production of multiple vaccines. One mechanism of potentially broadening or refocusing the immune response is to alter variable immunodominant epitopes on the pathogen potentially allowing for a more robust response to more conserved neutralizing epitopes. We will substitute various portions of the immunodominant G-H loop of VP1 in the Ad5-FMD vector with foreign epitopes and examine the ability of the redesigned vectors to induce cross neutralization of heterologous viruses within the same serotype. We will continue to develop improved Ad5-FMD vectors and as information is obtained from the above approaches the best candidates will be tested with the improved vector platforms.