Passive protection of mice and sheep against bluetongue virus by a neutralizing monoclonal antibody.

A murine hybridoma antibody, 6C2A.4.2, previously characterized as an immunoglobulin G class 2a that binds in radioimmunoassay to bluetongue virus serotype 17 (BTV-17) but not the other 19 BTV serotypes, neutralizes BTV-17, inhibits hemagglutination with BTV-17, and precipitates viral polypeptides 2 and 3 from BTV-17-infected cells, was produced as an ascites in the peritoneal cavities of hybridoma-inoculated mice. This ascitic fluid, but not those containing other, non-neutralizing anti-BTV-17 antibodies of the same isotype, provided serotype-specific passive protection against BTV-17-induced death of neonatal mice. Antibody 6C2A.4.2-containing ascitic fluid was injected intravenously into sheep that were later inoculated with BTV-17. These sheep remained free of clinical signs, did not develop viremia or detectable levels of antibodies reactive in the immunodiffusion test used for routine BTV diagnosis in the United States, and developed only low levels of neutralizing antibodies. Control animals became viremic and developed immunodiffusion test reactions and high levels of neutralizing antibodies during recovery, and two of three had lesions and fevers. These results provide evidence that antibodies directed against a single epitope on BTV-17 can prevent bluetongue disease.