Immune enhancement and attenuation of vaccinia virus recombinants expressing empty viral particles of SIV and lymphokines.

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Immune enhancement and attenuation of vaccinia virus recombinants expressing empty viral particles of SIV and lymphokines.

Symp Nonhum Primate Models AIDS. 1992 Nov 17-20;10:abstract no. 115. Unique Identifier : AIDSLINE PRIM10/93200953
Giavedoni LD; Parodi L; Ahmad S; Bassiri M; Yilma T; International Laboratory of Molecular Biology for Tropical; Disease Agents, University of California, Davis 95616.

Abstract: Simian immunodeficiency virus (SIV) infection in rhesus macaques is a model for human immunodeficiency virus (HIV) in humans. Limited protection against SIV has been demonstrated in rhesus macaques vaccinated with live attenuated or inactivated viral vaccine. However, the use of whole inactivated or live, virus vaccines have major safety concerns. To circumvent these problems, we have developed vaccinia virus (VV) and baculovirus recombinants that express SIV gag and env genes which produce immature retrovirus-like particles (VLPs). These VLPs have a close conformational resemblance to infectious virus and have the potential to provide a safe and effective vaccine against SIV. We have previously demonstrated that VV virulence can be attenuated by co-expression of IFN-gamma. Immunodeficient nude mice could clear an otherwise lethal VV infection when these recombinants express either MuIFN-gamma or a fusion protein of MuIFN-gamma and HIV structural proteins (Giavedoni et al, PNAS USA 89, 3409-3413, 1992). We have now developed a number of rVVs that co-express MuIFN-gamma and VLPs. Electron microscopic studies have shown the formation of VLPs in cells infected by all gag-expressing recombinants. MuIFN-gamma was also detected in the supernatant of infected cells 4-6 h post-infection when expressed by an early-late VV promotor and 8-10 h post-infection when a late promotor was used. A similar set of recombinants expressing human IFN-gamma have also been constructed, and antiviral activity has been demonstrated in Vero cells indicating that human IFN-gamma is active in monkeys. We are currently investigating the level of attenuation of these rVVs in nude mice and their potential to induce protective immunity against SIV in rhesus macaques.

Keywords: Animal Baculoviridae/*GENETICS Genes, env Genes, gag Human Interferon Type II/ANALYSIS/GENETICS/IMMUNOLOGY Lymphokines/GENETICS/*IMMUNOLOGY Macaca mulatta Mice Promoter Regions (Genetics) Recombination, Genetic Retroviridae/GENETICS SIV/*GENETICS Vaccines, Attenuated/*GENETICS/IMMUNOLOGY Vaccinia Virus/*GENETICS Vero Cells Viral Vaccines/*GENETICS/IMMUNOLOGY ABSTRACT
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