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Patterson, R; Eley, T S; Browne, C; Martineau, H M; Werling, D
Publisher: Elsevier BV
Journal: Vaccine
Languages: English
Types: Article
Subjects: veterinary(all), Immunology and Microbiology(all), Infectious Diseases, Molecular Medicine, PCV2b, Oral, Freeze-dried, ORF2, Article, Yeast, IFN?, Public Health, Environmental and Occupational Health
Porcine circovirus type 2 (PCV2) is now endemic in every major pig producing country, causing PCV-associated disease (PCVAD), linked with large scale economic losses. Current vaccination strategies are based on the capsid protein of the virus and are reasonably successful in preventing PCVAD but fail to induce sterile immunity. Additionally, vaccinating whole herds is expensive and time consuming. In the present study a ?proof of concept? vaccine trial was employed to test the effectiveness of powdered freeze-dried recombinant Saccharomyces cerevisiae yeast stably expressing the capsid protein of PCV2b on its surface as an orally applied vaccine. PCV2-free pigs were given 3 doses of vaccine or left un-vaccinated before challenge with a defined PCV2b strain. Rectal temperatures were measured and serum and faeces samples were collected weekly. At the end of the study, pigs were euthanized, tissue samples taken and tested for PCV2b load by qPCR and immunohistochemistry. The peak of viraemia in sera and faeces of unvaccinated pigs was higher than that of vaccinated pigs. Additionally more sIgA was found in faeces of vaccinated pigs than unvaccinated. Vaccination was associated with lower serum concentrations of TNF? and IL-1? but higher concentrations of IFN? and IFN? in comparison to the unvaccinated animals. At the end of the trial, a higher viral load was found in several lymphatic tissues and the ileum of unvaccinated pigs in comparison to vaccinated pigs. The difference between groups was especially apparent in the ileum. The results presented here demonstrate a possible use for recombinant S. cerevisiae expressing viral proteins as an oral vaccine against PCV2. A powdered freeze-dried recombinant S. cerevisiae used as an oral vaccine could be mixed with feed and may offer a cheap and less labour intensive alternative to inoculation with the additional advantage that no cooling chain would be required for vaccine transport and storage.
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    • [1] Allan GM, Mc Neilly F, Meehan BM, Kennedy S, Mackie DP, Ellis JA, et al. Isolation and characterisation of circoviruses from pigs with wasting syndromes in Spain, Denmark and Northern Ireland. Vet Microbiol 1999;66:115-23.
    • [2] Mavrommatis B, Offord V, Patterson R, Watson M, Kanellos T, Steinbach F, et al. Global gene expression profiling of myeloid immune cell subsets in response to in vitro challenge with porcine circovirus 2b. PLoS ONE 2014;9:e91081.
    • [3] Marcekova Z, Psikal I, Kosinova E, Benada O, Sebo P, Bumba L. Heterologous expression of full-length capsid protein of porcine circovirus 2 in Escherichia coli and its potential use for detection of antibodies. J Virol Methods 2009;162:133-41.
    • [4] Beach NM, Meng XJ. Efficacy and future prospects of commercially available and experimental vaccines against porcine circovirus type 2 (PCV2). Virus Res 2012;164:33-42.
    • [5] Gilligan CA, Li Wan Po A. Oral enteric vaccines - clinical trials. J Clin Pharm Ther 1991;16:309-35.
    • [6] Sedgmen BJ, Meeusen EN, Lofthouse SA. Alternative routes of mucosal immunization in large animals. Immunol Cell Biol 2004;82:10-6.
    • [7] Bucarey SA, Noriega J, Reyes P, Tapia C, Saenz L, Zuniga A, et al. The optimized capsid gene of porcine circovirus type 2 expressed in yeast forms virus-like particles and elicits antibody responses in mice fed with recombinant yeast extracts. Vaccine 2009;27:5781-90.
    • [8] Alarcon P, Velasova M, Mastin A, Nevel A, Stark KD, Wieland B. Farm level risk factors associated with severity of post-weaning multi-systemic wasting syndrome. Prev Vet Med 2011;101:182-91.
    • [9] Patterson R, Nevel A, Diaz AV, Martineau HM, Demmers T, Browne C, et al. Exposure to environmental stressors result in increased viral load and further reduction of production parameters in pigs experimentally infected with PCV2b. Vet Microbiol 2015;177:261-9.
    • [10] Franzusoff A, Duke RC, King TH, Lu Y, Rodell TC. Yeasts encoding tumour antigens in cancer immunotherapy. Expert Opin Biol Ther 2005;5:565-75.
    • [11] Huang H, Ostroff GR, Lee CK, Specht CA, Levitz SM. Robust stimulation of humoral and cellular immune responses following vaccination with antigenloaded beta-glucan particles. MBio 2010;1.
    • [12] Stubbs AC, Martin KS, Coeshott C, Skaates SV, Kuritzkes DR, Bellgrau D, et al. Whole recombinant yeast vaccine activates dendritic cells and elicits protective cell-mediated immunity. Nat Med 2001;7:625-9.
    • [13] Allnutt FC, Bowers RM, Rowe CG, Vakharia VN, LaPatra SE, Dhar AK. Antigenicity of infectious pancreatic necrosis virus VP2 subviral particles expressed in yeast. Vaccine 2007;25:4880-8.
    • [14] Sun H, Wang L, Wang T, Zhang J, Liu Q, Chen P, et al. Display of Eimeria tenella EtMic2 protein on the surface of Saccharomyces cerevisiae as a potential oral vaccine against chicken coccidiosis. Vaccine 2014;32:1869-76.
    • [15] Shin MK, Yoo HS. Animal vaccines based on orally presented yeast recombinants. Vaccine 2013;31:4287-92.
    • [16] Dvorak CM, Lilla MP, Baker SR, Murtaugh MP. Multiple routes of porcine circovirus type 2 transmission to piglets in the presence of maternal immunity. Vet Microbiol 2013;166:365-74.
    • [17] Wieland B, Werling D, Nevel A, Rycroft A, Demmers TG, Wathes CM, et al. Porcine circovirus type 2 infection before and during an outbreak of postweaning multisystemic wasting syndrome on a pig farm in the UK. Vet Rec 2012;170:596.
    • [18] Patterson R, Nerren J, Kogut M, Court P, Villarreal-Ramos B, Seyfert HM, et al. Yeast-surface expressed BVDV E2 protein induces a Th1/Th2 response in naive T cells. Dev Comp Immunol 2012;37:107-14.
    • [19] Signer EN, Jeffreys AJ, Licence S, Miller R, Byrd P, Binns R. DNA profiling reveals remarkably low genetic variability in a herd of SLA homozygous pigs. Res Vet Sci 1999;67:207-11.
    • [20] Grierson SS, King DP, Wellenberg GJ, Banks M. Genome sequence analysis of 10 Dutch porcine circovirus type 2 (PCV-2) isolates from a PMWS case-control study. Res Vet Sci 2004;77:265-8.
    • [21] O'Neill KC, Shen HG, Lin K, Hemann M, Beach NM, Meng XJ, et al. Studies on porcine circovirus type 2 vaccination of 5-day-old piglets. Clin Vaccine Immunol 2011;18:1865-71.
    • [22] Opriessnig T, Thacker EL, Yu S, Fenaux M, Meng XJ, Halbur PG. Experimental reproduction of postweaning multisystemic wasting syndrome in pigs by dual infection with Mycoplasma hyopneumoniae and porcine circovirus type 2. Vet Pathol 2004;41:624-40.
    • [23] Bilusic M, Heery CR, Arlen PM, Rauckhorst M, Apelian D, Tsang KY, et al. Phase I trial of a recombinant yeast-CEA vaccine (GI-6207) in adults with metastatic CEA-expressing carcinoma. Cancer Immunol Immunother 2014;63:225-34.
    • [24] Haller AA, Lauer GM, King TH, Kemmler C, Fiolkoski V, Lu Y, et al. Whole recombinant yeast-based immunotherapy induces potent T cell responses targeting HCV NS3 and Core proteins. Vaccine 2007;25:1452-63.
    • [25] Kim HJ, Lee JY, Kang HA, Lee Y, Park EJ. Oral immunization with whole yeast producing viral capsid antigen provokes a stronger humoral immune response than purified viral capsid antigen. Lett Appl Microbiol 2014;58:285-91.
    • [26] Lu Y, Bellgrau D, Dwyer-Nield LD, Malkinson AM, Duke RC, Rodell TC, et al. Mutation-selective tumor remission with Ras-targeted, whole yeast-based immunotherapy. Cancer Res 2004;64:5084-8.
    • [27] Fort M, Sibila M, Nofrarias M, Perez-Martin E, Olvera A, Mateu E, et al. Evaluation of cell-mediated immune responses against porcine circovirus type 2 (PCV2) Cap and Rep proteins after vaccination with a commercial PCV2 sub-unit vaccine. Vet Immunol Immunopathol 2012;150:128-32.
    • [28] Rodriguez-Arrioja GM, Segales J, Calsamiglia M, Resendes AR, Balasch M, PlanaDuran J, et al. Dynamics of porcine circovirus type 2 infection in a herd of pigs with postweaning multisystemic wasting syndrome. Am J Vet Res 2002;63:354-7.
    • [29] Sibila M, Calsamiglia M, Segales J, Blanchard P, Badiella L, Le Dimna M, et al. Use of a polymerase chain reaction assay and an ELISA to monitor porcine circovirus type 2 infection in pigs from farms with and without postweaning multisystemic wasting syndrome. Am J Vet Res 2004;65:88-92.
    • [30] Trible BR, Ramirez A, Suddith A, Fuller A, Kerrigan M, Hesse R, et al. Antibody responses following vaccination versus infection in a porcine circovirus-type 2 (PCV2) disease model show distinct differences in virus neutralization and epitope recognition. Vaccine 2012;30:4079-85.
    • [31] Fort M, Olvera A, Sibila M, Segales J, Mateu E. Detection of neutralizing antibodies in postweaning multisystemic wasting syndrome (PMWS)-affected and non-PMWS-affected pigs. Vet Microbiol 2007;125:244-55.
    • [32] Fort M, Fernandes LT, Nofrarias M, Diaz I, Sibila M, Pujols J, et al. Development of cell-mediated immunity to porcine circovirus type 2 (PCV2) in caesarean-derived, colostrum-deprived piglets. Vet Immunol Immunopathol 2009;129:101-7.
    • [33] Koinig HC, Talker SC, Stadler M, Ladinig A, Graage R, Ritzmann M, et al. PCV2 vaccination induces IFN-gamma/TNF-alpha co-producing T cells with a potential role in protection. Vet Res 2015;46:20.
    • [34] Engle TB, Jobman EE, Moural TW, McKnite AM, Bundy JW, Barnes SY, et al. Variation in time and magnitude of immune response and viremia in experimental challenges with Porcine circovirus 2b. BMC Vet Res 2015;10:286.
    • [35] Kreikemeier CA, Engle TB, Lucot KL, Kachman SD, Burkey TE, Ciobanu DC. Genome-wide analysis of TNF-alpha response in pigs challenged with porcine circovirus 2b. Anim Genet 2015;46:205-8.
    • [36] Liu G, Yang G, Guan G, Zhang Y, Ren W, Yin J, et al. Effect of dietary selenium yeast supplementation on porcine circovirus type 2 (PCV2) infections in mice. PLOS ONE 2015;10:e0115833.
    • [37] Fort M, Sibila M, Nofrarias M, Perez-Martin E, Olvera A, Mateu E, et al. Porcine circovirus type 2 (PCV2) Cap and Rep proteins are involved in the development of cell-mediated immunity upon PCV2 infection. Vet Immunol Immunopathol 2010;137:226-34.
    • [38] Seo HW, Han K, Park C, Chae C. Clinical, virological, immunological and pathological evaluation of four porcine circovirus type 2 vaccines. Vet J 2014;200:65-70.
    • [39] Seo HW, Oh Y, Han K, Park C, Chae C. Reduction of porcine circovirus type 2 (PCV2) viremia by a reformulated inactivated chimeric PCV1-2 vaccineinduced humoral and cellular immunity after experimental PCV2 challenge. BMC Vet Res 2012;8:194.
    • [40] Jiang T, Singh B, Li HS, Kim YK, Kang SK, Nah JW, et al. Targeted oral delivery of BmpB vaccine using porous PLGA microparticles coated with M cell homing peptide-coupled chitosan. Biomaterials 2014;35:2365-73.
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