Anti-idiotypic antibodies induce neutralizing antibodies to rabies virus glycoprotein

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Abstract
Rabbit anti-idiotypic antibodies (.alpha.Id Ab) were prepared against 5 murine monoclonal antibodies (mAb) specific for the rabies virus glycoprotein. Four of the mAb were directed against 3 known, type-specific, neutralizing sites on the glycoprotein, and the other mAb was directed against a topographically uncharacterized, nonneutralizing epitope. An absence of significant cross-reactivity among the .alpha.Id Ab for heterologous mAb suggested that the .alpha.Id Ab were highly specific for unique variable region determinants. The binding of 3 of the 5 .alpha.Id Ab to their homologous mAb could be inhibited by rabies virus-soluble glycoprotein, suggesting that the .alpha.Id Ab possessed subpopulations similar or adjacent to the antigen-binding site of the mAb. Two of the 5 .alpha.Id Ab injected into mice elicited a specific virus-neutralizing antibody response. Mechanisms to account for the induction of the virus-neutralizing antibody by .alpha.Id Ab are discussed.