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Title: Poly ICLC increases the potency of a replication-defective human adenovirus vectored foot-and-mouth disease vaccine

Author
item Diaz San Segundo, Fayna
item DIAS, CAMILA - Oak Ridge Institute For Science And Education (ORISE)
item MORAES, MAURO - University Of Connecticut
item WEISS, MARCELO - Oak Ridge Institute For Science And Education (ORISE)
item PEREZ-MARTIN, EVA - Oak Ridge Institute For Science And Education (ORISE)
item SALAZAR, ANDRES - Oncovir, Inc
item GRUBMAN, MARVIN - Retired ARS Employee
item De Los Santos, Teresa

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/14/2014
Publication Date: 11/1/2014
Citation: Diaz San Segundo, F.C., Dias, C.C., Moraes, M.P., Weiss, M., Perez-Martin, E., Salazar, A.M., Grubman, M.J., De Los Santos, T.B. 2014. Poly ICLC increases the potency of a replication-defective human adenovirus vectored foot-and-mouth disease vaccine. Virology. 468-470C:283-292.

Interpretive Summary: Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals. We have previously demonstrated that a replication-defective human adenovirus 5 vector carrying the FMDV capsid coding region of serotype A24 Cruzeiro (Ad5-CI-A24-2B) protects swine and cattle against FMDV challenge by 7 days post vaccination, allows serological differentiation of infected from vaccinated animals (DIVA) and manufacturing does not require a high containment facility. Despite the demonstrated efficacy and safety benefits of the Ad5-CI-A24-2B vaccine, higher production cost might limit its large scale use for outbreak control. In this study we have tested, for the first time, the adjuvant effect of poly ICLC, a molecule that induces several pathways of the innate immunity, when used in combination with Ad5-CI-A24-2B in swine. We found that the combination allowed us to reduce the vaccine protective dose by 80-fold. Interestingly, swine treated with the combination were protected against disease even in the absence of detectable FMDV-specific neutralizing antibodies at the time of challenge.

Technical Abstract: Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals. We have previously demonstrated that a replication-defective human adenovirus 5 vector carrying the FMDV capsid coding region of serotype A24 Cruzeiro (Ad5-CI-A24-2B) protects swine and cattle against FMDV challenge by 7 days post vaccination. However, since relatively large amounts of Ad5-CI-A24-2B are required to induce protection this strategy could be costly for livestock production. Poly ICLC is a synthetic double stranded RNA that activates multiple innate and adaptive immune pathways. In this study, we have tested for the first time, the adjuvant effect of poly ICLC in combination with Ad5-CI-A24-2B in swine. We found that the combination resulted in a reduction of the vaccine protective dose by 80-fold. Interestingly, the lowest dose of Ad5-CI-A24-2B plus 1 mg of poly ICLC protected against challenge even in the absence of detectable FMDV-specific neutralizing antibodies at the time of challenge.