IMMUNE PROTECTION CONFERRED BY THE BACULOVIRUS-RELATED GLYCOPROTEIN OF THOGOTO VIRUS (ORTHOMYXOVIRIDAE)

The coding region of segment 4 of Thogoto (THO) virus, a tickborne mem ber of the Orthomyxoviridae, was expressed in a baculovirus system und er the control of the polyhedrin promoter. This construct expressed au thentic envelope glycoprotein as determined by size and antigenic reac tivity with a panel of monoclonal antibodies (MAbs). Immunization of h amsters with Spodoptera frugiperda (Sf21) cells infected with the reco mbinant baculovirus induced neutralizing and protective antibodies aga inst virus challenge; control hamsters developed clinical disease with high-titer viremia 3 days postchallenge. In contrast to hamsters, gui nea pigs are comparatively resistant to THO virus infection but suppor t nonviremic transmission between cofeeding infected and uninfected ti cks. However, when uninfected ticks fed on guinea pigs immunized with the baculovirus recombinant, only 2% became infected following virus c hallenge of the animals compared to 26% of ticks on control nonimmune guinea pigs. Furthermore, neutralizing MAbs specific for THO viral gly coprotein protected mice against lethal challenge with THO virus; nonn eutralizing MAbs specific for the glycoprotein, which inhibit THO vira l agglutinating activity, did not induce a protective response. Thus a t least in the murine model, protective immunity is conferred by antib odies directed against the neutralizing epitope(s) of the baculovirus- related glycoprotein of THO virus. (C) 1995 Academic Press, Inc.