ELICITING HIV-1 ENVELOPE-SPECIFIC ANTIBODIES WITH MIXED VACCINIA VIRUS RECOMBINANTS

Recombinant vaccinia virus (VV) vectors that express the envelope (Env ) protein of the human immunodeficiency virus-type 1 (HIV-1) have been previously shown to elicit HIV-specific cytotoxic T-lymphocyte (CTL) and weak antibody responses in non-human primate studies and clinical trials. In first clinical trials, single Env proteins were presented t o the immune system by VV recombinants and other vectors, but individu als were not protected against later exposures to heterologous HIV. It is likely that the generation of protective immune responses against diverse HIV will require that vaccines encompass proteins from not jus t one, but multiple distinct HIV isolates. Here is described the simpl e construction of numerous new VV, each expressing a unique, truncated Env protein (VVenv). Mouse experiments were performed to evaluate the ability of these VVenv to elicit immune responses. HIV-1-specific ant ibodies appeared within one month following one intraperitoneal inocul ation of mice with single or mixed VVenv, reaching plateau levels by 4 months. The magnitude of antibody production was poor at the close of 10(5) p.f.u. VVenv per animal, but improved with increasing doses of VVenv up to 10(7) p.f.u. per animal The subcutaneous route of VV immun ization, previously proven safe in human trials, was also effective fo r administering VVenv. These results highlight the strengths of VV con structs as vehicles for the presentation of multiple HIV-1-Env protein s to the naive immune system. (C) 1997 Elsevier Science Ltd.