Protective oral vaccination against infectious bursal disease virus using the major viral antigenic protein VP2 produced in Pichia pastoris

• Published in: PloS one Vol. 8; no. 12; p. e83210
• Main Authors: Taghavian, Omid, Spiegel, Holger, Hauck, Rüdiger, Hafez, Hafez M, Fischer, Rainer, Schillberg, Stefan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.12.2013; Public Library of Science (PLoS)
• Subjects: Adjuvants, Immunologic - administration & dosage; Administration, Oral; Animal vaccines; Animals; Antibodies; Antibodies, Viral - biosynthesis; Antigens; Arabidopsis thaliana; Atrophy; B cells; Birnaviridae Infections - immunology; Birnaviridae Infections - pathology; Birnaviridae Infections - prevention & control; Birnaviridae Infections - virology; Bursa of Fabricius - drug effects; Bursa of Fabricius - immunology; Bursa of Fabricius - pathology; Bursa of Fabricius - virology; Capsid protein; Chickens; Chickens - virology; Cloning; Damage prevention; Disease; Dose-Response Relationship, Immunologic; Genetic engineering; Growth rate; Immune clearance; Immune response; Immune system; Immunoglobulins; Immunosuppression; Infectious bursal disease; Infectious bursal disease virus - immunology; Infectious diseases; Injections, Intramuscular; Lesions; Molecular biology; Oral administration; Pichia - genetics; Pichia pastoris; Poultry; Poultry Diseases - immunology; Poultry Diseases - pathology; Poultry Diseases - prevention & control; Poultry Diseases - virology; Proteins; RNA polymerase; Trichoplusia ni; Vaccination; Vaccines; Vaccines, Synthetic; Veterinary medicine; Viral proteins; Viral Structural Proteins - immunology; Viral Vaccines - administration & dosage; Viral Vaccines - immunology; Viruses; Yeast; Aachen Germany; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0083210

Infectious bursal disease virus (IBDV) causes economically important immunosuppressive disease in young chickens. The self-assembling capsid protein (VP2) from IBDV strain IR01 was expressed in Pichia pastoris resulting in the formation of homomeric, 23-nm infectious bursal disease subviral particles (IBD-SVPs) with a yield of 76 mg/l before and 38 mg/l after purification. Anti-IBDV antibodies were detected in chickens injected with purified IBD-SVPs or fed with either purified IBD-SVPs or inactivated P. pastoris cells containing IBD-VP2 (cell-encapsulated). Challenge studies using the heterologous classical IBDV strain (MB3) showed that intramuscular vaccination with 20 µg purified IBD-SVPs conferred full protection, achieved complete virus clearance and prevented bursal damage and atrophy, compared with only 40% protection, 0-10% virus clearance accompanied by severe atrophy and substantial bursal damage in mock-vaccinated and challenge controls. The commercial IBDV vaccine also conferred full protection and achieved complete virus clearance, albeit with partial bursal atrophy. Oral administration of 500 µg purified IBD-SVPs with and without adjuvant conferred 100% protection but achieved only 60% virus clearance with adjuvant and none without it. Moderate bursal damage was observed in both cases but the inclusion of adjuvant resulted in bursal atrophy similar to that observed with live-attenuated vaccine and parenteral administration of 20 µg purified IBD-SVPs. The oral administration of 250 mg P. pastoris cells containing IBD-VP2 resulted in 100% protection with adjuvant and 60% without, accompanied by moderate bursal damage and atrophy in both groups, whereas 25 mg P. pastoris cells containing IBD-VP2 resulted in 90-100% protection with moderate bursal lesions and severe atrophy. Finally, the oral delivery of 50 µg purified IBD-SVPs achieved 40-60% protection with severe bursal lesions and atrophy. Both oral and parenteral administration of yeast-derived IBD-VP2 can therefore induce a specific and protective immune response against IBDV without affecting the growth rate of chickens.