Recombinant human adenovirus-5 expressing capsid proteins of Indian vaccine strains of foot-and-mouth disease virus elicits effective antibody response in cattle

Authors: SREENIVASA, B - Indian Veterinary Research Institute; MOHAPATRA, J - Indian Council Of Agricultural Research-Directorate Of Foot And Mouth Disease; Pauszek, Steven; Koster, Marla; DHANYA, V - Indian Veterinary Research Institute; TAMIL SELVAN, R - Indian Veterinary Research Institute; HOSAMANI, M - Indian Veterinary Research Institute; SARAVANAN, P - Indian Veterinary Research Institute; BASAGOUDANAVAR, S - Indian Veterinary Research Institute; De Los Santos, Teresa; VENKATARAMANAN, R - Indian Veterinary Research Institute; Rodriguez, Luis; Grubman, Marvin

Submitted to: Veterinary Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/16/2017
Publication Date: 5/1/2017
Citation: Sreenivasa, B.P., Mohapatra, J.K., Pauszek, S.J., Koster, M.J., Dhanya, V.C., Tamil Selvan, R.P., Hosamani, M., Saravanan, P., Basagoudanavar, S.H., De Los Santos, T.B., Venkataramanan, R., Rodriguez, L.L., Grubman, M.J. 2017. Recombinant human adenovirus-5 expressing capsid proteins of Indian vaccine strains of foot-and-mouth disease virus elicits effective antibody response in cattle. Veterinary Microbiology. 203:196-201. doi: 10.1016/j.vetmic.2017.03.019.

Interpretive Summary: Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals. ARS scientists have previously developed a recombinant vaccine that uses a modified live replication-defective human adenovirus 5 vector to deliver FMDV proteins (Ad5-FMD). This vaccine has proven effective in swine and cattle, the two animal species of most interest in agriculture. For the first time in the last 50 years, this technology was licensed as an effective molecular vaccine against FMD in the US. In collaboration with colleagues at the Indian Veterinary Research Institute in Bengaluru, India, ARS has now generated Ad5-FMD vaccines against three viruses endemic in India: types A, O and Asia 1. These novel vaccines were evaluated for their capacity of inducing a predictive protective immune response in indigenous Indian cattle. While vaccination with the individual types induced a promising response, vaccination with the combination of the three was less effective. These results suggest that although promising, the Ad5-FMD technology in for India FMDV strains needs further improvement.

Technical Abstract: Recombinant adenovirus-5 vectored foot-and-mouth disease constructs (Ad5- FMD) were made for three Indian vaccine virus serotypes O,A and Asia 1. Constructs co-expressing foot-and- mouth disease virus (FMDV) capsid and viral 3C protease sequences, were evaluated for their ability to induce a neutralizing antibody response in indigenous cattle (Bos indicus). Purified Ad5-FMD viruses were inoculated in cattle as monovalent (5 x 109 pfu/animal) or trivalent (5 x 109 pfu/animal per serotype) vaccines. Animals vaccinated with monovalent AdS-FMD vaccines were boosted 63 days later with the same dose. After primary immunization, virus neutralization tests (VNT) showed seroconversion in 83, 67 and 33% of animals vaccinated with Ad5-FMD O,A and Asia 1, respectively. Booster immunization elicited seroconversion in all or the animals (100%) in the monovalent groups. When used in a trivalent form, the AdS-FMD vaccine induced neutralizing antibodies in only 33, 50 and 16% of animals against serotypes O,A and Asia 1,respectively on primo-vaccination, and titers were significantly lower than when the same vectors were used in monovalent form. Neutralizing antibody titers differed by serotype for both AdS­ FMD monovalent and trivalent vaccines, with Asia 1 serotype inducing the lowest titers. Antibody response to Ad5 vector in immunized cattle was also assessed by VNT. It appeared that the vector immunity did not impact the recall responses to expressed FMDV antigens on booster immunization. In summary, the study suggested that the recombinant Ad5-FMD vaccine has a potential use in monovalent form, while its application in multivalent form is not currently encouraging.