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.
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.
Plum Island Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, NAA, P.O. Box 848, Greenport, NY 11944, United States.
Mauro Pires
MP
Moraes
Fayna Diaz-San
FD
Segundo
Camila C
CC
Dias
Lindomar
L
Pena
Marvin J
MJ
Grubman
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D036022:Capsid Proteins / Q000276:immunology*; D002417:Cattle; D002418:Cattle Diseases; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics; D005536:Foot-and-Mouth Disease / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D011401:Promoter Regions, Genetic; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D022223:Vaccines, Subunit / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology / Q000627:therapeutic use; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D036022:Capsid Proteins; D022223:Vaccines, Subunit; D014764:Viral Proteins; D014765:Viral Vaccines