Recombinant Subunit Vaccine Candidate against the Bovine Viral Diarrhea Virus

Author:

Avello Verónica1ORCID,Salazar Santiago1ORCID,González Eddy E.2ORCID,Campos Paula1,Manríque Viana1ORCID,Mathieu Christian3,Hugues Florence4ORCID,Cabezas Ignacio4ORCID,Gädicke Paula4ORCID,Parra Natalie C.1,Acosta Jannel1,Sánchez Oliberto5,González Alaín6,Montesino Raquel1

Affiliation:

1. Biotechnology and Biopharmaceuticals Laboratory, Pathophysiology Department, School of Biological Sciences, Universidad de Concepción, Víctor Lamas 1290, Concepción P.O. Box 160C, Chile

2. Department of Medicine, Division of Gastroenterology, Miller School of Medicine, University of Miami, Miami, FL 33146, USA

3. Virology Section of the SAG’s Sub-Department Network of Animal Health Laboratories, Lo Aguirre, Santiago de Chile 9020000, Chile

4. Pathology and Preventive Medicine Department, School of Veterinary Sciences, Universidad de Concepción, Vicente Méndez 595, Chillán P.O. Box 537, Chile

5. Pharmacology Department, School of Biological Sciences, Universidad de Concepción, Victor Lamas 1290, Concepción P.O. Box 160C, Chile

6. Faculty of Basic Sciences, University of Medellin, Cra. 87 No 30-65, Medellin 050026, Colombia

Abstract

Multivalent live-attenuated or inactivated vaccines are often used to control the bovine viral diarrhea disease (BVD). Still, they retain inherent disadvantages and do not provide the expected protection. This study developed a new vaccine prototype, including the external segment of the E2 viral protein from five different subgenotypes selected after a massive screening. The E2 proteins of every subgenotype (1aE2, 1bE2, 1cE2, 1dE2, and 1eE2) were produced in mammalian cells and purified by IMAC. An equimolar mixture of E2 proteins formulated in an oil-in-water adjuvant made up the vaccine candidate, inducing a high humoral response at 50, 100, and 150 µg doses in sheep. A similar immune response was observed in bovines at 50 µg. The cellular response showed a significant increase in the transcript levels of relevant Th1 cytokines, while those corresponding to the Th2 cytokine IL-4 and the negative control were similar. High levels of neutralizing antibodies against the subgenotype BVDV1a demonstrated the effectiveness of our vaccine candidate, similar to that observed in the sera of animals vaccinated with the commercial vaccine. These results suggest that our vaccine prototype could become an effective recombinant vaccine against the BVD.

Funder

Scientific and Technological Development Support Fund

Publisher

MDPI AG

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