MUCOSAL IMMUNIZATION WITH RECOMBINANT ADENOVIRUSES - INDUCTION OF IMMUNITY AND PROTECTION OF COTTON RATS AGAINST RESPIRATORY BOVINE HERPESVIRUS TYPE-1 INFECTION

To facilitate the evaluation of vaccines against bovine herpesvirus ty pe 1 (BHV-1), a cotton rat model of intranasal (i.n.) BHV-1 infection was established, Cotton rat lung cells were similar to bovine cells in their ability to support BHV-1 replication in vitro. Furthermore, i.n . inoculation of cotton rats with BHV-1 resulted in pulmonary lesions comparable to BHV-1 infection in cattle. Using this model, the potenti al of i.n. and gastrointestinal (g.i,) immunization was examined with recombinant human adenoviruses expressing glycoprotein D (go) of BHV-1 to induce protective immunity against BHV-1. The replication-competen t virus (gD-dE3) was more efficient than the replication-defective vir us (gD-dE1E3) in inducing gD-specific antibody in the serum and in the respiratory tract. Furthermore, i.n. immunization with gD-dE3 stimula ted antigen-specific antibody-secreting cells in the lung 12 weeks fol lowing immunization. Protection against BHV-1 challenge correlated wit h go-specific antibody levels such that i.n. immunization with gD-dE3 conferred complete protection, while g.i. immunization conferred only partial protection of the lungs of most animals against BHV-1 challeng e. In comparison, immunization with gD-dE1E3 by either route resulted in only a partial reduction of BHV-1 titre in the respiratory tract. T he results obtained demonstrate that mucosal immunization with replica tion-competent recombinant adenovirus expressing go of BHV-1 can induc e immunity and protection against BHV-1 challenge.