Abstract

Attenuated variants of vaccinia virus have excellent potential for the construction of safe recombinant live vaccines. In this investigation, highly attenuated variants of vaccinia virus with several genetic markers and a variant recombinant were tested in Balb/c mice for their ability to induce humoral immune response. Mice primed with variants that had an 8-MDa deletion at the left end of the viral genome induced similar levels of circulating anti-vaccinia antibodies as the wild-type virus. However, mice primed with variants that had several genetic lesions (deletions and point mutations) induced lower levels of circulating anti-vaccinia antibodies. Mice primed and boosted with a recombinant variant with several genetic lesions, and containing the complete envelope gene of the human immunodeficiency virus (HIV) and the bacterial beta-galactosidase (beta-gal) gene, induced significant antibody response to gp 160 and beta-gal. The antibody response to gp 160 was markedly increased by successive inoculations with the recombinant variant. Our findings provide evidence that the extent of activation of the immune system by vaccinia variants can be modulated by the nature of the virus genetic lesion. In addition, when these variants are used as recombinant vaccines, it is possible to induce low levels of circulating anti-vaccinia antibodies after priming and yet achieve significant antibody response to virus-expressed foreign antigens, even after repeated boosters. Such variants could be useful in the design of live recombinant viruses as safe vaccines.