Safety profile of a replication-deficient human adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle

Transbound Emerg Dis. 2018 Apr;65(2):447-455. doi: 10.1111/tbed.12724. Epub 2017 Oct 27.

Abstract

The safety of a replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was evaluated in five independent safety studies. The target animal safety studies were designed in compliance with United States (U.S.) regulatory requirements (Title 9, U.S. Code of Federal Regulation [9CFR]) and international standard guidelines (VICH Topic GL-44) for veterinary live vaccines. The first three studies were conducted in a total of 22 vaccinees and demonstrated that the AdtA24 master seed virus (MSV) was safe, did not revert to virulence and was not shed or spread from vaccinees to susceptible cattle or pigs. The fourth safety study conducted in 10 lactating cows using an AdtA24 vaccine serial showed that the vaccine was completely absent from milk. The fifth safety study was conducted under typical U.S. production field conditions in 500 healthy beef and dairy cattle using two AdtA24 vaccine serials. These results demonstrated that the vaccine was safe when used per the product label recommendations. Additional data collected during these five studies confirmed that AdtA24 vaccinees developed FMDV A24 and the HAd5 vaccine vector serum neutralization antibodies that test negative in a FMDV non-structural protein antibody test, confirming AdtA24 vaccine's capability to differentiate infected from vaccinated animals (DIVA). In conclusion, results from this comprehensive set of cattle studies demonstrated the safety of the replication-deficient AdtA24 vaccine and fulfilled safety-related requirements for U.S. regulatory requirements.

Keywords: foot-and-mouth disease virus; regulatory; replication-deficient human adenovirus; safety; vaccine.

MeSH terms

  • Adenoviruses, Human / genetics*
  • Animals
  • Antibodies, Viral / blood
  • Capsid Proteins / genetics
  • Cattle
  • Cattle Diseases / immunology
  • Cattle Diseases / prevention & control*
  • Cattle Diseases / virology
  • Female
  • Foot-and-Mouth Disease / immunology
  • Foot-and-Mouth Disease / prevention & control*
  • Foot-and-Mouth Disease / virology
  • Foot-and-Mouth Disease Virus / genetics
  • Foot-and-Mouth Disease Virus / immunology*
  • Genetic Vectors*
  • Humans
  • Lactation
  • Male
  • Neutralization Tests
  • Serogroup
  • Swine
  • Vaccination
  • Vaccines, Subunit
  • Viral Vaccines / administration & dosage*
  • Viral Vaccines / adverse effects

Substances

  • Antibodies, Viral
  • Capsid Proteins
  • Vaccines, Subunit
  • Viral Vaccines