INDUCTION OF SYSTEMIC AND MUCOSAL IMMUNE-RESPONSES IN COTTON RATS IMMUNIZED WITH HUMAN ADENOVIRUS TYPE-5 RECOMBINANTS EXPRESSING THE FULL AND TRUNCATED FORMS OF BOVINE HERPESVIRUS TYPE-1 GLYCOPROTEIN GD

We generated both replication-incompetent (HAdB-SD-E1 and HAd5-tSD-E1) and replication-competent (HAd5-gD-E3 and HAd5-tgD-E3) human adenovir us type 5 (HAdB) recombinants expressing the full (go) or truncated fo rm (gD) of the glycoprotein go gene of bovine herpevirus type 1 (BHV-1 ). Recombinant go and tgD expressed by HAd5-gD-E1 and HAd5-gD-E3 and b y HAd5-tgD-E1 and HAdS-tgD-E3, respectively, were recognized by gD-spe cific monoclonal antibodies (MAbs) directed against linear and conform ational epitopes, suggesting that antigenicity of recombinant go and t gD was similar to that of the native go expressed in BHV-1 infected ce lls. In HAd5-SD-E1- or HAd5-gD-E3-inoculated cotton rats there was a s trong gD- and HAd5-specific IgG and IgA antibody response. The immune response was significantly lower in animals similarly immunized with H Ad5-tgD-E1 or HAd5-tgD-E3, indicating that live adenovirus vaccine vec tors may be better suited to the full-length form of glycoprotein go t han its truncated form. After a BHV-1 challenge, no infectious BHV-1 v irions were isolated from the trachea of cotton rats previously immuni zed with HAd5-gD-E1 or HAd5-gD-E3. These results suggest that adenovir us E1 insertion (replication-incompetent) and E3 insertion (replicatio n-competent) vectors have excellent potential for use in developing li ve recombinant virus vaccines and provide evidence that the cotton rat model can be used in BHV1 vaccination-challenge trials. (C) 1996 Acad emic Press, Inc.