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 i ncidence 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 D1 7 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 probabl y, natural killer cell recognition; however, we have tested the possib ility that this domain is not required for inducing an adaptive, prote ctive immune response. Immunization of calves with this truncated gpl protein induced gpI-specific nasal IgA, IgG1, serum neutralizing antib odies and gpI-specific peripheral lymphocyte proliferation. All immuni zed calves were protected from clinical disease after BHV-1 challenge. Further, nine of ten immunized calves had no intranasal viral sheddin g. One animal shed a minimal amount of virus following challenge, but produced no antibodies to other viral proteins as evidenced by immunop recipitation of S-35-labelled viral proteins by sera from virus-challe nged animals. This study represents the first evidence that a recombin ant truncated gpI subunit vaccine can confer local mucosal immunity an d 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 v accinated from wild-type virus-infected animals.