Resistance to bovine respiratory syncytial virus (BRSV) induced in calves by a recombinant bovine herpesvirus-1 expressing the attachment glycoprotein of BRSV

Abstract

The ability of a bovine herpesvirus-1 (BHV-1) recombinant expressing the G protein of bovine respiratory syncytial virus (BRSV) to protect against BRSV infection was examined in calves. A synthetic G gene was inserted behind the gE promoter of BHV-1 to give a gE-negative, BHV-1/G recombinant. Gnotobiotic calves, vaccinated intranasally and intratracheally with BHV-1/G were challenged 6 weeks later with the Snook strain of BRSV. As controls, calves were vaccinated with a gE-negative mutant of BHV-1 which contains a frame-shift (BHV-1/gEfs). Whereas infection with BHV-1/gEfs induced only mild clinical signs, infection with BHV-1/G resulted in more severe clinical disease and higher titres of BHV-1/G were isolated from the lungs when compared with BHV-1/gEfs. Thus, expression of the G protein of BRSV increased the virulence of BHV-1 for calves. Vaccination with BHV-1/G induced BRSV-specific antibody in serum and respiratory secretions. However, only one calf developed low levels of BRSV complement-dependent neutralizing antibody. Although BHV-1/G primed calves for BRSV-specific lymphocyte proliferative responses, there was no evidence for priming of BRSV-specific cytotoxic T cells. After challenge with BRSV, there was a significant reduction in nasopharyngeal excretion of BRSV in BHV-1/G-vaccinated calves compared with controls and BRSV was isolated from the lung of only one of five vaccinated calves compared with all four control animals. In addition, the extent of gross pneumonic lesions 7 days after BRSV challenge was significantly reduced in calves vaccinated with BHV-1/G compared with controls given BHV-1/gEfs.