Inclusion of the bovine neutrophil beta-defensin 3 with glycoprotein D of bovine herpesvirus 1 in a DNA vaccine modulates immune responses of mice and cattle.
Bovine herpesvirus 1 (BoHV-1) causes recurrent respiratory and genital infections in cattle and predisposes them to lethal secondary infections. While modified live and killed BoHV-1 vaccines exist, these are not without problems. Development of an effective DNA vaccine for BoHV-1 has the potential to address these issues. As a strategy to enhance DNA vaccine immunity, a plasmid encoding the bovine neutrophil beta-defensin 3 (BNBD3) as a fusion with truncated glycoprotein D (tgD) and a mix of two plasmids encoding BNBD3 and tgD were tested in mice and cattle. In mice, coadministration of BNBD3 on the separate plasmid enhanced the tgD-induced gamma interferon (IFN-γ) response but not the antibody response. BNBD3 fused to tgD did not affect the antibody levels or the number of IFN-γ-secreting cells but increased the induction of tgD-specific cytotoxic T lymphocytes (CTLs). In cattle, the addition of BNBD3 as a fusion construct also modified the immune response. While the IgG and virus-neutralizing antibody levels were not affected, the number of IFN-γ-secreting cells was increased after BoHV-1 challenge, specifically the CD8(+) IFN-γ(+) T cells, including CD8(+) IFN-γ(+) CD25(+) CTLs. While reduced virus shedding, rectal temperature, and weight loss were observed, the level of protection was comparable to that observed in pMASIA-tgD-vaccinated animals. These data show that coadministration of BNBD3 with a protective antigen as a fusion in a DNA vaccine strengthened the Th1 bias and increased cell-mediated immune responses but did not enhance protection from BoHV-1 infection.
VIDO-Intervac, University of Saskatchewan, Saskatoon, Canada.
Sarah
S
Mackenzie-Dyck
Jennifer
J
Kovacs-Nolan
Marlene
M
Snider
Lorne A
LA
Babiuk
Sylvia
S
van Drunen Littel-van den Hurk
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D001831:Body Temperature; D001835:Body Weight; D002417:Cattle; D002418:Cattle Diseases / Q000517:prevention & control*; D006566:Herpesviridae Infections / Q000517:prevention & control / Q000662:veterinary*; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*; D017201:Virus Shedding; D023083:beta-Defensins / Q000235:genetics / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014764:Viral Proteins; D023083:beta-Defensins; C046998:bovine herpesvirus type-1 glycoproteins; D007371:Interferon-gamma