Vaccine 29 (2011) 9431–9440 Contents lists available at SciVerse ScienceDirect Vaccine jou rn al h om epa ge: www.elsevier.com/locate/vaccine Increased efficacy of an adenovirus-vectored foot-and-mouth disease capsid subunit vaccine expressing nonstructural protein 2B is associated with a specific T cell response Mauro Pires Moraes a,b , Fayna Diaz-San Segundo a,c , Camila C. Dias a,c , Lindomar Pena a,c,1 , Marvin J. Grubman a,∗ a Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, NAA, P.O. Box 848, Greenport, NY 11944, United States b Department of Pathobiology and Veterinary Sciences, University of Connecticut, Storrs, CT, United States c Oak Ridge Institute for Science and Education, PIADC Research Participation Program, Oak Ridge, TN 37831, United States a r t i c l e i n f o Article history: Received 4 August 2011 Received in revised form 6 October 2011 Accepted 16 October 2011 Available online 24 October 2011 Keywords: Foot-and-mouth disease virus Replication-defective human adenovirus vectored vaccines FMDV protein 2B T cell response FMDV serotype O1 Campos a b s t r a c t We previously demonstrated that an adenovirus-based foot-and-mouth disease virus (FMDV) serotype A24 capsid subunit vaccine, Ad5-A24, expressed under the control of a cytomegalovirus promoter (CMV) can protect swine and bovines against homologous challenge, but in a similar approach using swine vaccinated with an Ad5-vectored FMDV O1 Campos vaccine, Ad5-O1C, the animals were only partially protected when challenged at 21 days post-vaccination (dpv). Recently, we demonstrated that inclusion of the complete coding region of nonstructural protein 2B in the Ad5-A24 vector resulted in improved immune responses in pigs. We also found that inclusion of a modified CMV promoter (pCI), Ad5-CI-A24- 2B, enhanced the efficacy of the vector. To address the limited immunogenicity of Ad5-O1C, we have produced a new set of Ad5 vectors with the complete 2B coding region under the control of either the original or the modified version of the CMV promoter, Ad5-O1C-2B, or Ad5-CI-O1C-2B, respectively. To evaluate the potency and efficacy of the new vectors we performed 2 sets of experiments in cattle. In the first experiment we compared the original vector with vectors containing the pCI promoter and partial or full-length 2B. All groups were challenged, intradermally in the tongue, at 21 dpv with FMDV O1C. We found that in all vaccinated groups 2 of 4 animals were protected from clinical disease. In the second experiment we directly compared the efficacy of vectors with a partial or full-length 2B under the control of the original CMV promoter. While all animals in the control group developed clinical disease, 2 of 4 animals in the group receiving Ad5-O1C vaccine and 3 of 4 animals in the group receiving Ad5- O1C-2B vaccine were completely protected after challenge. We also observed a 100-fold reduction of virus shedding in Ad5-O1C vaccinated animals and the group receiving Ad5-O1C-2B had an additional 10-fold reduction compared with the Ad5-O1C vaccinated group. There was no difference in the level of neutralizing antibodies in the vaccinated groups. However, we detected a significant antigen specific- CD4 + and CD8 + T cell response as early as 1 day post-challenge (dpc) in both Ad5-O1C and Ad5-O1C- 2B groups. Interestingly, the group receiving Ad5-O1C-2B had a statistically significant higher antigen specific-CD4 + and CD8 + T cell response at 5 dpc and 3 and 5 dpc, respectively, as compared to the Ad5-O1C inoculated group. These results indicate that inclusion of the complete 2B coding region improves the efficacy of Ad5 vaccines against FMDV serotype O and induces specific-CD4 + and CD8 + T cell responses that correlate with protection. Published by Elsevier Ltd. ∗ Corresponding author. Tel.: +1 631 323 3329; fax: +1 631 323 3006. E-mail address: marvin.grubman@ars.usda.gov (M.J. Grubman). 1 Current address: Virginia-Maryland Regional College of Veterinary Medicine, College Park, MD 20742, United States. 1. Introduction Foot-and-mouth disease (FMD) is considered one of the most contagious and economically devastating diseases affecting cloven- hoofed livestock worldwide [1–4]. FMD is characterized by fever, lameness and the appearance of vesicular lesions on the mouth, tongue, nose, feet and teats [3,4]. The etiologic agent, FMD virus (FMDV), has a positive-sense, single-stranded RNA genome and belongs to the genus Aphthovirus 0264-410X/$ – see front matter Published by Elsevier Ltd. doi:10.1016/j.vaccine.2011.10.037