Manipulation of Vaccinia Virus Vectors

Vaccinia virus has been used to express many diverse genes, such as prokaryotic enzymes, eukaryotic growth factors, protozoan structural proteins, and >50 different virus gene products (for reviews, see refs. 1–3 ). The widespread use of vaccinia virus as a vector owes much to the ease of generating recombinants, the authenticity of the foreign gene product, and the wide variety of uses to which they have been put. For example, HIV 1 (human immunodeficiency virus) envelope glycoprotein expressed by a vaccinia recombinant is biologically and antigenically indistinguishable from the authentic glycoprotein (4 –bi7 ). Recombinants have been used to generate HIV-neutralizing antibody (4 –6 ) to immunize animals and humans (8 –10 ), and to analyze cytotoxic T-cell and antibody-dependent cellular cytotoxicity (11 –13 ). Furthermore, the antigenicity of HIV enu has been improved by site-directed mutagenesis of protease cleavage sites (14 ).