TRUNCATED BOVINE HERPESVIRUS-1 GLYCOPROTEIN I (GPI) INITIATES A PROTECTIVE LOCAL IMMUNE-RESPONSE IN ITS NATURAL HOST

Current modified live and killed BHV-1 vaccines have not reduced the incidence of bovine herpesvirus-1 (BHV-1), the principal viral agent in bovine respiratory disease complex. The requirement for production of viral proteins for immune study has resulted in the establishment of a cell line which constitutively expresses BHV-1 gpI. A truncated BHV-1 envelope gpI protein was secreted into the culture supernatant of D17 cells transfected with the gpI gene lacking the coding sequence for the transmembrane region (TMR). The transmembrane domain is essential for gpl stability in the envelope, virus infectivity and, most probably, natural killer cell recognition; however, we have tested the possibility that this domain is not required for inducing an adaptive, protective immune response. Immunization of calves with this truncated gpl protein induced gpI-specific nasal IgA, IgG1, serum neutralizing antibodies and gpI-specific peripheral lymphocyte proliferation. All immunized calves were protected from clinical disease after BHV-1 challenge. Further, nine of ten immunized calves had no intranasal viral shedding. One animal shed a minimal amount of virus following challenge, but produced no antibodies to other viral proteins as evidenced by immunoprecipitation of S-35-labelled viral proteins by sera from virus-challenged animals. This study represents the first evidence that a recombinant truncated gpI subunit vaccine can confer local mucosal immunity and establish a strong protective barrier against disease caused by BHV-1 in the natural host. Also, these data demonstrate the feasibility of preventing initial viral replication in the host and distinguishing vaccinated from wild-type virus-infected animals.