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.

摘要

Bovine herpesvirus 1 (BoHV-1) causes recurrent respiratory and genital infectionsin cattle and predisposes them to lethal secondary infections. While modifiedlive and killed BoHV-1 vaccines exist, these are not without problems.Development of an effective DNA vaccine for BoHV-1 has the potential to addressthese issues. As a strategy to enhance DNA vaccine immunity, a plasmid encodingthe bovine neutrophil beta-defensin 3 (BNBD3) as a fusion with truncatedglycoprotein D (tgD) and a mix of two plasmids encoding BNBD3 and tgD were testedin mice and cattle. In mice, coadministration of BNBD3 on the separate plasmidenhanced the tgD-induced gamma interferon (IFN-γ) response but not the antibodyresponse. 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 Tlymphocytes (CTLs). In cattle, the addition of BNBD3 as a fusion construct alsomodified the immune response. While the IgG and virus-neutralizing antibodylevels were not affected, the number of IFN-γ-secreting cells was increased afterBoHV-1 challenge, specifically the CD8(+) IFN-γ(+) T cells, including CD8(+)IFN-γ(+) CD25(+) CTLs. While reduced virus shedding, rectal temperature, andweight loss were observed, the level of protection was comparable to thatobserved 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 enhanceprotection from BoHV-1 infection.