Inclusion of a specific T cell epitope increases the protection conferred against foot-and-mouth disease virus in pigs by a linear peptide containing an immunodominant B cell site

Virology Journal

Esther Blanco²  Francisco Sobrino¹  David Andreu³  Juan Bárcena²  Beatriz G de la Torre³  Carolina Cubillos² 

[1] Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Cantoblanco, 28049 Madrid, Spain;Centro de Investigación en Sanidad Animal (CISA-INIA), Carretera de Algete a El Casar, Valdeolmos, 28130 Madrid, Spain;Departament de Ciències Experimentals i de la Salut, Universitat Pompeu-Fabra, 08003 Barcelona, Spain

关键词: Swine;    Pig;    Vaccine;    Linear peptides;    FMDV;    Foot-and-mouth disease virus;   

Others  :  1154877
DOI  :  10.1186/1743-422X-9-66

 received in 2011-10-17, accepted in 2012-03-14,  发布年份 2012

【 摘 要 】

Background

Foot-and-mouth disease virus (FMDV) causes an economically important and highly contagious disease of cloven-hoofed animals. FMD control in endemic regions is implemented using chemically inactivated whole-virus vaccines. Currently, efforts are directed to the development of safe and marked vaccines. We have previously reported solid protection against FMDV conferred by branched structures (dendrimeric peptides) harbouring virus-specific B and T-cell epitopes. In order to gain insights into the factors determining a protective immune response against FMDV, in this report we sought to dissect the immunogenicity conferred by different peptide-based immunogens. Thus, we have assessed the immune response and protection elicited in pigs by linear peptides harbouring the same FMDV B-cell or B and T-cell epitopes (B and TB peptides, respectively).

Results

Pigs were twice immunized with either the B-cell epitope (site A) peptide or with TB, a peptide where the B-cell epitope was in tandem with the T-cell epitope [3A (21-35)]. Both, B and TB peptides were able to induce specific humoral (including neutralizing antibodies) and cellular immune responses against FMDV, but did not afford full protection in pigs. The data obtained showed that the T-cell epitope used is capable to induce efficient T-cell priming that contributes to improve the protection against FMDV. However, the IgA titres and IFNγ release elicited by these linear peptides were lower than those detected previously with the dendrimeric peptides.

Conclusions

We conclude that the incorporation of a FMDV specific T-cell epitope in the peptide formulation allows a significant reduction in virus excretion and clinical score after challenge. However, the linear TB peptide did not afford full protection in challenged pigs, as that previously reported using the dendrimeric construction indicating that, besides the inclusion of an adecuate T-cell epitope in the formulation, an efficient presentation of the B-cell epitope is crucial to elicit full protection by peptide vaccines.

【 授权许可】

   
2012 Cubillos et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]James AD, Rushton J: The economics of foot and mouth disease. Rev Sci Tech 2002, 21:637-644.
• [2]Rodriguez LL, Grubman MJ: Foot and mouth disease virus vaccines. Vaccine 2009, 27(Suppl 4):D90-D94.
• [3]Valarcher JF, Leforban Y, Rweyemamu M, Roeder PL, Gerbier G, Mackay DK, Sumption KJ, Paton DJ, Knowles NJ: Incursions of foot-and-mouth disease virus into Europe between 1985 and 2006. Transbound Emerg Dis 2008, 55:14-34.
• [4]Sumption K, Rweyemamu M, Wint W: Incidence and distribution of foot-and-mouth disease in Asia, Africa and South America; combining expert opinion, official disease information and livestock populations to assist risk assessment. Transbound Emerg Dis 2008, 55:5-13.
• [5]Leforban Y, Gerbier G: Review of the status of foot and mouth disease and approach to control/eradication in Europe and Central Asia. Rev Sci Tech 2002, 21:477-492.
• [6]Foot-and-Mouth disease situation worldwide and major epidemiological events in 2005-2006 [http://www.fao.org/docs/eims/upload//225050/Focus_ON_1_07_en.pdf] webcite
• [7]Doel TR: FMD vaccines. Virus Res 2003, 91:81-99.
• [8]Cottam EM, Wadsworth J, Shaw AE, Rowlands RJ, Goatley L, Maan S, Maan NS, Mertens PP, Ebert K, Li Y, et al.: Transmission pathways of foot-and-mouth disease virus in the United Kingdom in 2007. PLoS Pathog 2008, 4:e1000050.
• [9]Grubman MJ: Development of novel strategies to control foot-and-mouth disease: marker vaccines and antivirals. Biologicals 2005, 33:227-234.
• [10]Kitching P, Hammond J, Jeggo M, Charleston B, Paton D, Rodriguez L, Heckert R: Global FMD control-is it an option? Vaccine 2007, 25:5660-5664.
• [11]Acharya R, Fry E, Stuart D, Fox G, Rowlands D, Brown F: The three-dimensional structure of foot-and-mouth disease virus at 2.9 A resolution. Nature 1989, 337:709-716.
• [12]Bittle JL, Houghten RA, Alexander H, Shinnick TM, Sutcliffe JG, Lerner RA, Rowlands DJ, Brown F: Protection against foot-and-mouth disease by immunization with a chemically synthesized peptide predicted from the viral nucleotide sequence. Nature 1982, 298:30-33.
• [13]van der Burg SH, Bijker MS, Welters MJ, Offringa R, Melief CJ: Improved peptide vaccine strategies, creating synthetic artificial infections to maximize immune efficacy. Adv Drug Deliv Rev 2006, 58:916-930.
• [14]Pasick J: Application of DIVA vaccines and their companion diagnostic tests to foreign animal disease eradication. Anim Health Res Rev 2004, 5:257-262.
• [15]Taboga O, Tami C, Carrillo E, Nunez JI, Rodriguez A, Saiz JC, Blanco E, Valero ML, Roig X, Camarero JA, et al.: A large-scale evaluation of peptide vaccines against foot-and-mouth disease: lack of solid protection in cattle and isolation of escape mutants. J Virol 1997, 71:2606-2614.
• [16]Sobrino F, Saiz M, Jimenez-Clavero MA, Nunez JI, Rosas MF, Baranowski E, Ley V: Foot-and-mouth disease virus: a long known virus, but a current threat. Vet Res 2001, 32:1-30.
• [17]Cubillos C, de la Torre BG, Jakab A, Clementi G, Borras E, Barcena J, Andreu D, Sobrino F, Blanco E: Enhanced mucosal immunoglobulin A response and solid protection against foot-and-mouth disease virus challenge induced by a novel dendrimeric peptide. J Virol 2008, 82:7223-7230.
• [18]Blanco E, Garcia-Briones M, Sanz-Parra A, Gomes P, De Oliveira E, Valero ML, Andreu D, Ley V, Sobrino F: Identification of T-cell epitopes in nonstructural proteins of foot-and-mouth disease virus. J Virol 2001, 75:3164-3174.
• [19]Leclerc C: New approaches in vaccine development. Comp Immunol Microbiol Infect Dis 2003, 26:329-341.
• [20]Rowlands D: Foot-and-mouth disease virus peptide vaccines. In Foot-and-Mouth disease: Current perspectives. Edited by Sobrino F, Domingo E. Norfolk: Horizon Bioscience; 2004:335-354.
• [21]Purcell AW, McCluskey J, Rossjohn J: More than one reason to rethink the use of peptides in vaccine design. Nat Rev Drug Discov 2007, 6:404-414.
• [22]Brun A, Barcena J, Blanco E, Borrego B, Dory D, Escribano JM, Le Gall-Recule G, Ortego J, Dixon LK: Current strategies for subunit and genetic viral veterinary vaccine development. Virus Res 2011, 157:1-12.
• [23]Borrego B, Fernandez-Pacheco P, Ganges L, Domenech N, Fernandez-Borges N, Sobrino F, Rodriguez F: DNA vaccines expressing B and T cell epitopes can protect mice from FMDV infection in the absence of specific humoral responses. Vaccine 2006, 24:3889-3899.
• [24]Borrego B, Argilaguet JM, Perez-Martin E, Dominguez J, Perez-Filgueira M, Escribano JM, Sobrino F, Rodriguez F: A DNA vaccine encoding foot-and-mouth disease virus B and T-cell epitopes targeted to class II swine leukocyte antigens protects pigs against viral challenge. Antivir Res 2011, 92:359-363.
• [25]Black L, Francis MJ, Rweyemamu MM, Umebara O, Boge A: The relationship between serum antibody titres and protection from foot and mouth disease in pigs after oil emulsion vaccination. J Biol Stand 1984, 12:379-389.
• [26]McCullough KC, De Simone F, Brocchi E, Capucci L, Crowther JR, Kihm U: Protective immune response against foot-and-mouth disease. J Virol 1992, 66:1835-1840.
• [27]McCullough KC, Sobrino F: Immunology of Foot-and-Mouth disease. In Foot-and-Mouth disease: Current perspectives. Edited by Sobrino F, Domingo E. Norfolk: Horizon Bioscience; 2004:173-222.
• [28]Mateu MG, Verdaguer N: Functional and structural aspects of the interaction of foot-and-mouth disease virus with antibodies. In Foot-and-Mouth disease: Current perspectives. Edited by Sobrino F, Domingo E. Norfolk: Horizon Bioscience; 2004:223-260.
• [29]Eble PL, Bouma A, Weerdmeester K, Stegeman JA, Dekker A: Serological and mucosal immune responses after vaccination and infection with FMDV in pigs. Vaccine 2007, 25:1043-1054.
• [30]Jennings GT, Bachmann MF: Designing recombinant vaccines with viral properties: a rational approach to more effective vaccines. Curr Mol Med 2007, 7:143-155.
• [31]O'Shea , Jhon J, Nutman , Thomas B: Immunoregulation. [http://www.els.net] webciteeLS John Wiley & Sons Ltd, Chichester; 2001. doi:10.1038/npg.els.0000952
• [32]Zhang ZD, Hutching G, Kitching P, Alexandersen S: The effects of gamma interferon on replication of foot-and-mouth disease virus in persistently infected bovine cells. Arch Virol 2002, 147:2157-2167.
• [33]Nunez JI, Molina N, Baranowski E, Domingo E, Clark S, Burman A, Berryman S, Jackson T, Sobrino F: Guinea pig-adapted foot-and-mouth disease virus with altered receptor recognition can productively infect a natural host. J Virol 2007, 81:8497-8506.
• [34]Alves MP, Guzylack-Piriou L, Juillard V, Audonnet JC, Doel T, Dawson H, Golde WT, Gerber H, Peduto N, McCullough KC, Summerfield A: Innate immune defenses induced by CpG do not promote vaccine-induced protection against foot-and-mouth disease virus in pigs. Clin Vaccine Immunol 2009, 16:1151-1157.
• [35]Golding SM, Hedger RS, Talbot P: Radial immuno-diffusion and serum-neutralisation techniques for the assay of antibodies to swine vesicular disease. Res Vet Sci 1976, 20:142-147.
• [36]Saiz M, De La Morena DB, Blanco E, Nunez JI, Fernandez R, Sanchez-Vizcaino JM: Detection of foot-and-mouth disease virus from culture and clinical samples by reverse transcription-PCR coupled to restriction enzyme and sequence analysis. Vet Res 2003, 34:105-117.