Animal and Veterinary Sciences
Volume 6, Issue 6, November 2018, Pages: 95-101
Received: Dec. 11, 2018;
Accepted: Jan. 2, 2019;
Published: Jan. 31, 2019
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Eva Perozo, Research and Development Department, HIPRA, Amer, Spain
Joaquim Mallorquí, Research and Development Department, HIPRA, Amer, Spain
Ainhoa Puig, Research and Development Department, HIPRA, Amer, Spain
David Sabaté, Research and Development Department, HIPRA, Amer, Spain
Laura Ferrer-Soler, Research and Development Department, HIPRA, Amer, Spain
Ricard March, Research and Development Department, HIPRA, Amer, Spain
The aim of this study was to evaluate under field conditions the efficacy and safety of Vepured, a new recombinant vaccine against Edema Disease in pigs. The study was conducted on five commercial farrow-to-finish pig farms, which had historical records of clinical signs and presented F18-positive E.coli producing VT2e. The study was designed as a multicenter, randomized, placebo-controlled, blinded field trial comparing Vepured vaccine to a placebo (phosphate-buffered saline). Animals, at the age of 2-3 days, were administered intramuscularly with 1mL of Vepured (n=945) or with 1mL of phosphate-buffered saline (n=824). After product administration, animals were followed-up until slaughter. During this period, several efficacy and safety parameters were evaluated. On each farm, animals from both groups were held in the same unit and subjected to the same husbandry practices throughout the study. Clinical outbreaks of edema disease were only reported on four farms. On these farms, vaccination with Vepured resulted in a statistically significant reduction in both the mortality rate and the occurrence of clinical signs related to the disease. A statistically significantly higher mean growth performance was also reported in the vaccinated group compared to the placebo group. In the farm without clinical outbreak of edema disease differences were also observed in growth performance in favor of the vaccinated group. No systemic reactions were observed during or immediately after vaccination with Vepured. Only mild transient local reactions, and slight clinically non-relevant temperature increases were reported in some animals. The results obtained in this study demonstrate that vaccination with Vepured is safe and efficacious against naturally occurring edema disease infection.
A Multicenter, Randomized Field Trial on the Efficacy and Safety of VEPURED®, A New Vaccine Against Edema Disease in Pigs, Animal and Veterinary Sciences.
Vol. 6, No. 6,
2018, pp. 95-101.
Fairbrother J. M. and Gyles C. 2012. Disease of swine, 10th. eds. Zimmerman J. J., Karriker L. A., Ramirez A., Schwartz K. J. and Stevenson G. W. Ames, Iowa. Chap 53 (Colibacilosis), 723-749.
Casanova N. A., Redondo L. M., Dailoff G. C., Arenas D. and Fernández Miyakawa M. E. 2018. Overview of the role of Shiga toxins in porcine edema disease pathogenesis. Toxicon. 15: 148-154.
Bergan J., Dyve Lingelem A. B., Simm R., Skotland T. and Sandwig K. 2012. Shiga toxins. Toxicon, 60(6): 1085-1107.
Clugston R. E., Nielsen N. O. and Smith D. L. T. 1974. Experimental edema disease of swine (E. coli enterotoxemia) III. Pathology and pathogenesis. Can J Comp Med, 38: 34-43.
MacLeod D. L., Gyles C. L. and Wilcock B. P. 1991. Reproduction of oedema disease of swine with purified Shiga-like toxin-II variant. Vet Pathol, 28: 66–73.
Bosworth B. T., Samuel J. E., Moon H. W., O'brien A. D., Gordon V. M. and Whipp S. C. 1996. Vaccination with genetically modified Shiga-like toxin IIe prevents oedema disease in swine. Infect Immun, 64: 55-60.
Bosworth B. T., Green R. A. and Morrison R. B. 1994. Oedema disease: A search for a genetic link. J Swine Health Prod, 2(3): 19-22.
Teuber M. 2001. Veterinary use and antibiotic resistence. Curr Opin Microbiol, 4: 493-499
Phillips I., Casewell M., Cox T., de Groot B., Friis C., Jones R., Nightingale C., Preston R. and Waddell J. 2004. Does the use of antibiotics in food animals pose a risk to human health? A critical review of published data. J. Antimicrob Chemother, 53: 28-52.
Kusumoto M., Hidoka Y., Fujii Y., Murata M., Miyoshi H., Ogura Y., Gotoh Y., Iwata T., Hayashi T. and Akiba M. 2016. Emergence of a Multidrug-Resistant Shiga Toxin-Producing Enterotoxigenic Escherichia coli Lineage in Diseased Swine in Japan. J Clin Microbiol, 54(4): 1074-1081.
Bednorz C., Oelgeschläger K., Kinnemann B., Hartmann S., Neumann K., Pieper R., et al. 2013 The broader context of antibiotic resistance: zinc feed supplementation of piglets increases the proportion of multi-resistant Escherichia coli in vivo. Intl J Medical Microbiol. 303: 396–403.
Won G., John Hwa L. 2017. Potent immune responses induced by a Salmonella ghost delivery system that expresses the recombinant Stx2eB, FedF, and FedA proteins of the Escherichia coli-producing F18 and Shiga toxin in a murine model and evaluation of its protective effect as a porcine vaccine candidate. Vet Q. 37(1): 81-90.
Toshio S., Takeshi M., Eiji T., Yumiko K., Sou-Ichi M., Ko K., Kazutoshi S. and Takashi H. 2013. Evaluation of Recombinant Forms of the Shiga Toxin Variant Stx2eB Subunit and Non-Toxic Mutant Stx2e as Vaccine Candidates against Porcine Edema Disease. J Vet Med Sci. 75(10): 1309–1315.
Oanh T. K., Nguyen V. K., de Greve H. and Goddeeris B. M. 2012. Protection of piglets against oedema disease by maternal immunization with Stx2e toxoid. Infect Immun, 80: 469–73.
European Medicines Agency. 2013. CVMP assessment report for ECOPORC SHIGA. Retrieved 04/12/2018 from https://www.ema.europa.eu/documents/assessment-report/ecoporc-shiga-epar-public-assessment-report_en.pdf.
European Medicines Agency. 2017. CVMP assessment report for VEPURED. Retrieved 04/12/2018 from https://www.ema.europa.eu/documents/assessment-report/vepured-epar-public-assessment-report_en.pdf.
Mallorquí J., Simon-Grifé M., Ferrer-Soler L., Roca M., March R. and Sitjà M. 2018. Reduced mortality and morbidity associated with verotoxin 2e-induced edema disease in pigs using a recombinant verotoxin 2e vaccine. J. Swine Health Prod. 26(5): 253-261.
VICH GL9 (Good Clinical Practice) June 2000 - Implemented in July 2001. Retrieved 18/06/2018 from https://vichsec.org/guidelines/pharmaceuticals/pharma-efficacy/good-clinical-practice.
. Zhang W., Zhao M., Ruesch L., Omot A. and Francis D. 2007. Prevalence of virulence genes in Escherichia coli strains recently isolated from young pigs with diarrhea in the US. Vet Microbiol, 123: 145-152.
Badiella L. and Marino A. P. 2005. Cálculo del tamaño muestral ™ con el programa Ene 2.0: manual del programa, documentación y ejemplos. eds. Gráficas Monterreina. Spain, Madrid.
Johansen M., Andresen L. O., Jorsal S. E., Thomsen L. K., Waddell T. E. and Gyles C. L. 1997. Prevention of oedema disease in pigs by vaccination with verotoxin 2e toxoid. Can J Vet Res, 61: 280-285.
Fricke R., Bastert O., Gotter V., Brons N., Kamp J. and Selbitz H. J. 2015. Implementation of a vaccine against Shigatoxin 2e in a piglet producing farm with problems of Oedema disease: case study. Porcine Health Management, 1: 6.
Gordon N. A., Whipp S. C., Moon H. W., O'Brien A. D. and Samuels J. E. 1992. An enzymatic mutant of Shiga-like toxin-II variant is a vaccine candidate for oedema disease of swine. Infect Immun, 60: 485-490.
Makino S. I., Watarai M., Tabuchi H., Shirahata T., Furuoka H., Kobayashi Y. and Takeda Y. 2001. Genetically modified Shiga toxin 2e (Stx2e) producing Escherichia coli is a vaccine candidate for porcine oedema disease. Microb Pathog, 31: 1– 8.
Gannon V. P., Gyles C. L. and Wilcock B. P. 1989. Effects of Escherichia coli Shiga-like toxins (verotoxins) in pigs. Can J Vet Res, 53: 306-312.