Efficacy of an adenovirus-vectored foot-and-mouth disease virus serotype A subunit vaccine in cattle using a direct contact transmission model

Background: A direct contact transmission challenge model was used to simulate natural foot-and-mouth disease virus (FMDV) spread from FMDV A24/Cruzeiro/BRA/55 infected 'seeder' steers to naive or vaccinated steers previously immunized with a replication-deficient human adenovirus-vectored FMDV A24/Cruzeiro/BRA/55 capsid-based subunit vaccine (AdtA24). In two independent vaccine efficacy trials, AdtA24 was administered once intramuscularly in the neck 7 days prior to contact with FMDV A24/Cruzeiro/BRA/55-infected seeder steers. Results: In Efficacy Study 1, we evaluated three doses of AdtA24 to estimate the 50%/90% bovine protective dose (BPD50/90) for prevention of clinical FMD. In vaccinated, contact-challenged steers, the BPD 51(50/90) was 3.1 x 10(10 )/ 55 x 10(10) AdtA24 particles formulated without adjuvant. In Efficacy Study 2, steers vaccinated with 5 x 10(10) AdtA24 particles, exposed to FMDV A24/Cruzeiro/BRA/55-infected seeder steers, did not develop clinical FMD or transmit FMDV to other vaccinated or naive, non-vaccinated steers. In contrast, naive, non-vaccinated steers that were subsequently exposed to FMDV A24/Cruzeiro/BRA/55-infected seeder steers developed clinical FMD and transmitted FMDV by contact to additional naive, non-vaccinated steers. The AdtA24 vaccine differentiated infected from vaccinated animals (DIVA) because no antibodies to FMDV nonstructural proteins were detected prior to FMDV exposure. Conclusions: A single dose of the AdtA24 non-adjuvanted vaccine conferred protection against clinical FMD at 7 days post-vaccination following direct contact transmission from FMDV-infected, naive, non-vaccinated steers. The AdtA24 vaccine was effective in preventing FMDV transmission from homologous challenged, contact-exposed, AdtA24-vaccinated, protected steers to co-mingled, susceptible steers, suggesting that the vaccine may be beneficial in reducing both the magnitude and duration of a FMDV outbreak in a commercial cattle production setting.