Neutralizing antibodies in persistent borna disease virus infection: Prophylactic effect of gp94-specific monoclonal antibodies in preventing encephalitis

Borna disease virus (BDV) infection triggers an immune-mediated encephalomy elitis and results in a persistent infection. The immune response in the ac ute phase of the disease is characterized by a cellular response in which C D8(+) T cells are responsible for the destruction of virus-infected brain c ells. CD4(+) T cells function as helper cells and support the production of antiviral antibodies. Antibodies generated in the acute phase of the disea se against the nucleoprotein and the phosphoprotein are nonneutralizing. In the chronic phase of the disease, neutralizing antibodies directed against the matrix protein and glycoprotein are synthesized. In the present work, the biological role of the neutralizing-antibody response to BDV was furthe r investigated. By analyzing the blood of rats infected intracerebrally wit h BDV, a highly neurotropic virus, nucleic acid could be detected between 3 0 and 50 days after infection. Neutralizing antibodies were found between 6 0 and 100 days after infection. Furthermore, we produced hybridomas secreti ng BDV-specific neutralizing monoclonal antibodies. These antibodies, direc ted against the major glycoprotein (gp94) of BDV, were able to prevent Born a disease if given prophylactically. These data suggest that the late appea rance of BDV-specific neutralizing antibodies is due to the presence of BDV in the blood of chronically infected rats. Furthermore, these antibodies h ave the potential to neutralize the infectious virus when given early, whic h is an important finding with respect to the development of a vaccine.