A subunit gIV vaccine, produced by transfected mammalian cells in culture, induces mucosal immunity against bovine herpesvirus-1 in cattle

• Published in: Vaccine Vol. 12; no. 14; pp. 1295 - 1302
• Main Authors: van Drunen Littel-van den Hurk, S., Van Donkersgoed, J., Kowalski, J., van den Hurk, J.V., Harland, R., Babiuk, L.A., Zamb, T.J.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 1994; Elsevier
• Subjects: Animals; Antibodies, Viral - biosynthesis; Antibodies, Viral - blood; Biological and medical sciences; Blotting, Western - veterinary; Bovine herpesvirus-I; Cattle; Cattle Diseases - immunology; Cattle Diseases - prevention & control; Cell Line; Enzyme-Linked Immunosorbent Assay - veterinary; Fundamental and applied biological sciences. Psychology; Herpesviridae Infections - immunology; Herpesviridae Infections - prevention & control; Herpesviridae Infections - veterinary; Herpesvirus 1, Bovine - immunology; Microbiology; mucosal immunity; Nasal Mucosa - immunology; Neutralization Tests - veterinary; recombinant glycoprotein IV; Transfection; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - biosynthesis; Vaccines, Synthetic - immunology; Viral Proteins - administration & dosage; Viral Proteins - biosynthesis; Viral Proteins - immunology; Viral Vaccines - immunology; Virology; Bovine herpesvirus-I; recombinant glycoprotein IV; mucosal immunity; Immunoprotection; Immunization; Bovine; Secretion; Herpesviridae; Alphaherpesvirinae; Bovine herpesvirus 1; Glycoproteins; Vaccine; Subunit; Virus; Vertebrata; Mammalia; Transfection; Artiodactyla; Ungulata; Humoral immunity
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(94)80055-5

A truncated version of bovine herpesvirus-1 (BHV-1) glycoprotein 1 V (tgIV V) was produced in a novel, non-destructive expression system based upon regulation of gene expression by the bovine heat-shock protein 70A (hsp70) gene promoter in Madin Dal-by bovine kidney (MDBK) cells. In this system, up to 20 μg ml −1 of secreted tgIV, which is equivalent to the yield from 4 × 10 6 cells, was produced daily over a period of up to 18 days. Different doses of tgIV were injected intramuscularly into seronegative calves. Virus-neutralizing antibodies were induced by all doses of tgIV, both in the serum and in the nasal superficial mucosa. However, the low dose (2.3 μg) induced significantly ( p < 0.05) lower antibody titres than the medium (7 μg) and high (21 μg) doses. The medium and high doses of tgIV conferred protection from BHV-1 infection, as demonstrated by a significant ( p < 0.05) reduction in clinical signs of respiratory disease and virus shedding in the nasal secretions postchallenge. However, the 2.3,ug group, although partially protected, was not significantly ( p > 0.05) different from the placebo group. This study demonstrated the potential of an intramuscularly administered tgIV subunit vaccine to induce mucosal immunity to BHV-1 using an economic protein production system and an acceptable vaccine formulation. In addition, a strong correlation was observed between neutralizing antibodies in the serum and nasal superficial mucosa, virus shedding and clinical disease. Thus, serum neutralizing antibody levels in tgIV-immunized animals may be a good prognosticator of protection from BHV-1 infection and disease.