Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/1/2003
Publication Date: 12/12/2003
Citation: MORAES, M.P., CHINSANGARAM, J., BRUM, M.C., GRUBMAN, M.J. IMMEDIATE PROTECTION OF SWINE FROM FOOT-AND-MOUTH DISEASE: A COMBINATION OF ADENOVIRUSES EXPRESSING INTERFERON ALPHA AND A FOOT-AND-MOUTH DISEASE VIRUS SUBUNIT VACCINE. VACCINE. v22(2): 268-279, 2003. Interpretive Summary: Foot-and-mouth disease virus (FMDV) causes an economically devastating disease of cloven-hoofed animals. Vaccines produced by chemical inactivation of virus are available, but there are concerns about their safety and they do not induce protection prior to about 7 days postvaccination. In the event of an FMD outbreak in a disease-free country such as the US, it is necessary to induce immediate protection. We have shown that in cell culture FMDV replication is inhibited by type I interferon. Based on this information, we developed a recombinant human adenovirus as an expression vector that contains the gene for porcine interferon alpha. Swine given one inoculation of this recombinant virus and then challenged with virulent FMDV one day postinoculation were completely protected from clinical and serological signs of disease indicating sterile protection. These results demonstrated, for the first time, that a single inoculation of an Ad5-interferon virus could be used as a tool to immediately control FMD in emergency outbreak situations. In the current manuscript, we have extended these results and demonstrated that Ad5-interferon virus alone could protect swine for as long as five days postinoculation. Furthermore, a combination of Ad5-interferon and an Ad5-FMDV subunit vaccine could induce immediate as well as long-term protection. In the event of an FMD outbreak, this strategy may enable countries to avoid large-scale slaughter of animals and the subsequent environmental and social concerns that arise.
Technical Abstract: We have previously shown that swine inoculated with recombinant, replication-defective human adenovirus type 5 containing the porcine interferon alpha (Ad5-pIFN ) gene are completely protected when challenged one day later with virulent foot-and-mouth disease virus (FMDV). In the current study, we examined the duration of protection afforded swine by Ad5-pIFN and the ability of a combination of Ad5-pIFN and a FMDV subunit vaccine delivered by Ad5-A24 (an Ad5 vector containing the capsid coding region of FMDV serotype A24 Cruzeiro and the 3C proteinase coding region of serotype A12) to induce immediate as well as long-lasting protection against homologous FMDV challenge. Groups of swine were inoculated with Ad5-pIFN and challenged with virulent FMDV A24 1, 3, 5, and 7 days postinoculation (dpi) or 1 day preinoculation. All animals challenged 1 and 3 dpi were completely protected from disease. In the group challenged 5 dpi, one animal was completely protected and the other animals had significantly delayed and reduced disease. The animals in the remaining two groups had either no clinical signs of disease or clinical signs were delayed and less severe compared to the control group. Swine inoculated with a combination of Ad5-pIFN and Ad5-A24 and challenged 5 dpi were all completely protected from disease and developed a significant FMDV-specific neutralizing antibody response. This combination strategy has potential for rapid and long-lasting control of FMD as well as other acute viral diseases.