Protective immunity of gene-deleted SHIVs having an HIV-1 Env against challenge infection with a gene-intact SHIV

We constructed three simian-human immunodeficiency viruses (SHIVs) lacking regulatory gene(s) and analyzed their induction of protective immunity agai nst challenge infection with gene-intact SHIV in rhesus macaques. Inoculati on of SHIV-dn lacking nef and SHIV-drn lacking nef and vpr induced transien t viremia, while that of SHIV-dxrn lacking nef, vpr, and vps induced no vir emia. The SHIVs with fewer deletions were more effective in inducing neutra lizing antibodies and cytotoxic T lymphocyte responses. When these macaques were challenged with parental gene-intact SHIV-NM-3rN, all the SHIV-dn-vac cinated macaques and two of the four SHIV-drn-vaccinated macaques showed co mplete resistance. The other two SHIV-drn-vaccinated macaques and all SHIV- dxrn-vaccinated macaques did not show complete resistance, but they did sho w suppression of replication of the challenge virus. These results suggeste d that as more genes were deleted, protective immunity was decreased.