New developments in the pre- and post-exposure treatment of rabies.

Two approaches have been made to develop the alleged "second generation rabies vaccines". One utilizes recombinant DNA, expressing the G protein gene in a heterotypic host, the vaccinia virus, and has proven efficacious in protecting animals from rabies infection. The second approach posits that only a portion of the native viral antigen may be required to induce protective response. To define regions of the subunit molecule recognized by different immune effectors, epitopes on the G protein and nucleoprotein were identified which are recognized by B and T cells. These epitopes were delineated using chemically or enzymatically cleaved fragments of the native antigens or overlapping synthetic peptides covering the entire antigenic amino acid sequence. Protein fragments or synthetic peptides evincing antigenic activity were tested for ability to induce virus-specific immune responses in vivo. Immunization with synthetic peptides carrying epitopes for B and T cells conferred solid protection against lethal rabies virus infection.