Neutralizing and protective antibodies directed against vaccinia virus envelope antigens

The infection mechanism of vaccinia virus is largely unknown. Neither the a ttachment protein of extracellular enveloped virus (EEV), the biologically relevant infectious form of the virus, nor its cellular receptor has been i dentified. Surprisingly, all former attempts using antibodies to block EEV infection of cells in vitro had failed. Here, we report the production of a n anti-envelope hyperimmune serum with EEV neutralizing activity and show t hat a polyclonal antiserum against the extraviral domain of protein B5R als o inhibited EEV infection. in vivo, mice vaccinated with B5R protein were p rotected against a lethal vaccinia virus challenge. This protectivity is li kely to be mediated by neutralizing antibodies. Protein A33R, but not A34R and A36R, also proved to be protective in active and passive vaccination ex periments. However, in contrast to B5R, A33R protectivity did not correlate with antibody titers. Because anti-A33R antibodies did not neutralize EEV in vitro, the protectivity mediated by A33R protein probably involves a mec hanism different from simple antibody binding. Taken together, our results suggest that antibodies to a specific protective epitope or epitopes on pro tein B5R are able to prevent EEV infection. The protein encoded by the B5R gene is therefore likely to play a crucial role in the initial steps of vac cinia virus infection-binding to a host cell and entry into its cytoplasm. (C) 1999 Academic Press.