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The safety and efficacy of an experimental, replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was examined in eight independent cattle studies. AdtA24 non-adjuvanted vaccine was administered intramuscularly to a total of 150 steers in doses ranging from approximately 1.0×10(8) to 2.1×10(11) particle units per animal. No detectable local or systemic reactions were observed after vaccination. At 7 days post-vaccination (dpv), vaccinated and control animals were challenged with FMDV serotype A24 Cruzeiro via the intradermal lingual route. Vaccine efficacy was measured by FMDV A24 serum neutralizing titers and by protection from clinical disease and viremia after challenge. The results of eight studies demonstrated a strong correlation between AdtA24 vaccine dose and protection from clinical disease (R(2)=0.97) and viremia (R(2)=0.98). There was also a strong correlation between FMDV A24 neutralization titers on day of challenge and protection from clinical disease (R(2)=0.99). Vaccination with AdtA24 enabled differentiation of infected from vaccinated animals (DIVA) as demonstrated by the absence of antibodies to the FMDV nonstructural proteins in vaccinates prior to challenge. Lack of AdtA24 vaccine shedding after vaccination was indicated by the absence of neutralizing antibody titers to both the adenovector and FMDV A24 Cruzeiro in control animals after co-mingling with vaccinated cattle for three to four weeks. In summary, a non-adjuvanted AdtA24 experimental vaccine was shown to be safe, immunogenic, consistently protected cattle at 7 dpv against direct, homologous FMDV challenge, and enabled differentiation of infected from vaccinated cattle prior to challenge.

The results of the first decade of the development of a replication-defective human adenovirus serotype 5 (Ad5) containing the capsid- and 3C protease-coding regions of foot-and-mouth disease (FMD) virus as a vaccine candidate are presented. In proof-of-concept studies, it was demonstrated that a single inoculation with this vaccine vector containing the capsid of FMD virus A24 Cruzeiro protected both swine and cattle following homologous challenge by direct inoculation 1 week postvaccination. We have expanded these studies in cattle with larger numbers of animals and by testing the vaccine in direct-contact challenge studies, including its ability to prevent FMD virus shedding and transmission. Furthermore, we have developed manufacturing protocols to allow the scalable production of these FMD molecular vaccine products for US Department of Agriculture licensure approval and availability for inclusion in the US National Veterinary Stockpile. We have also constructed and initiated cattle efficacy testing of Ad5 vectors containing the capsid-coding regions from other FMD virus serotypes and subtypes, as well as initiated studies to improve FMD molecular vaccine potency.