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Title: Evaluation of fiber-modified adenovirus vector-vaccine against foot-and-mouth diseaes in cattle

Author
item MONTIEL, NESTOR - Oak Ridge Institute For Science And Education (ORISE)
item Medina, Gisselle
item STURZA, DIEGO - Oak Ridge Institute For Science And Education (ORISE)
item DIAZ-SAN SEGUNDO, FAYNA - University Of Connecticut
item RAMIREZ-MEDINA, ELIZABETH - Oak Ridge Institute For Science And Education (ORISE)
item Grubman, Marvin
item De Los Santos, Teresa

Submitted to: Clinical and Vaccine Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/5/2015
Publication Date: 2/1/2016
Citation: Montiel, N., Medina, G.N., Sturza, D., Diaz-San Segundo, F., Ramirez-Medina, E., Grubman, M.J., De Los Santos, T.B. 2016. Evaluation of fiber-modified adenovirus vector-vaccine against foot-and-mouth diseaes in cattle. Clinical and Vaccine Immunology. 23:125-136. doi: 10.1128/CVI.00426-15.

Interpretive Summary: Foot-and-mouth disease virus (FMDV) causes an economically devastating disease of cloven-hoofed animals. In recent years we have developed a novel vaccine that uses human adenovirus (Ad5-FMD) to deliver virus-like particles in animals. In fact we have demonstrated that this vaccine induces a fully protective response in swine and cattle against challenge with FMDV of some particular types but not others. It has been published that changing the coating of adenovirus may increase the vaccine targeting and allow for infection of immune cells resulting on a better immune response. In the current study we evaluated if an Ad5 vector that was modified in the fiber protein of its capsid could improve vaccine performance in vivo. Our results suggested that the modification of the vector does not enhance vaccine performance in cattle despite the induction of significant cell-mediated immunity and improved performance in vitro. This information is important for future design of better FMD vaccines.

Technical Abstract: Novel vaccination approaches against foot-and-mouth-disease (FMD) include the use of a replication-defective human adenovirus type 5 vector (Ad5) that contains the capsid encoding regions of FMD virus (FMDV). An Ad5.A24 has proven effective as a vaccine against FMD in swine and cattle. However, there is a need to increase efficacy, reduce costs, and demonstrate that such an approach is effective for all FMDV serotypes. We have previously demonstrated that an Ad5-vectored FMDV serotype O1 Campos vaccine (Ad5.O1C.2B) can partially protect bovines against homologous challenge when used alone. In the current study we assessed the efficacy of a fiber-modified Ad5 vector genetically engineered to express an Arg-Gly-Asp (RGD) (Adt.O1C.2B.RGD). Expression of FMDV capsid proteins was superior in cultured cells infected with the RGD-modified vector. Furthermore, transgene expression of Adt.O1C.2B.RGD was enhanced in cell lines that constitutively express integrin alpha v Beta 6. In animal studies our data showed that similarly to animals inoculated with the unmodified vector, animals vaccinated with the RGD vector were partially protected from challenge. Although none of the vaccinated animals had detectable viremia at any time-point of the study, viral nucleic acids (FMDV RNA) were detected in serum of animals with clinical signs. Interestingly, in animals vaccinated with Adt.O1C.2B.RGD, CD4+ and CD8+ IFN'+ cell responses were detected at statistically significant higher levels when compared to animals vaccinated with Ad5.O1C.2B. Our results suggest that inclusion of an RGD motif in the fiber of an Ad5 FMD vaccine vector improves transgene delivery and cell mediated immunity but does not significantly enhance vaccine performance in cattle.