|DIAZ SAN-SEGUNDO, FAYNA|
Submitted to: American Society for Virology Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 4/12/2007
Publication Date: 7/14/2007
Citation: Pena, L., Koster, M.J., Diaz San-Segundo, F., Grubman, M.J., 2007, Delivery of Both Foot-and-Mouth Disease Virus Structural and Nonstructural Antigens Improves Protection of Swine. American Society for Virology Meeting. W52-10, p.50.
Technical Abstract: Foot-and-mouth disease virus (FMDV) is the etiological agent of one of the most contagious diseases affecting cloven-hoofed animals and is the most important constraint on trade in live animals and animal products. The current vaccine has limitations when used in disease-free countries including difficulty in unambiguously differentiating vaccinated from infected animals and the need for costly, high-containment facilities for vaccine production. We have previously developed an alternative strategy that overcomes these disadvantages using a replication-defective human adenovirus type 5 (Ad5) vector that contains the coding regions for the FMDV A24 structural protein precursor and the 3C protease (Ad5-A24), a viral enzyme required for capsid polyprotein processing. One dose of this vaccine protects both swine and cattle as early as 7 days. In the present study, we added the coding regions of FMDV nonstructural proteins (NSPs) 2B and 2C to enhance the immunogenicity of the vaccine. In cell culture studies the new vectors, Ad5-A24+2B and Ad5-A24+2BC, expressed both the capsid and NSPs. In a vaccine test, four groups of swine were inoculated with Ad5-Blue (negative control), Ad5-A24, Ad5-A24+2B, and Ad5-A24+2BC. Twenty-one days post-vaccination all animals were challenged by direct inoculation with FMDV. This challenge was extremely severe since one control animal died 3 days after inoculation while the other control developed severe FMD and had high titer of virus in blood and nasal swabs. The animals vaccinated with either Ad5-A24 or Ad5-A24+2BC had less severe clinical signs, reduced virus shedding in nasal swabs and no detectable viremia. One swine out of three in both groups were completely protected from disease. Interestingly, all swine inoculated with Ad5-A24+2B had the highest neutralizing antibody response after vaccination, had no viremia or virus in nasal secretions, and were totally protected against FMDV challenge. These results indicate that addition of the 2B coding region to the Ad5-A24 vector provides an enhanced antibody response and complete protection from clinical disease.