IMMUNE-RESPONSES BUT NO PROTECTION AGAINST SHIV BY GENE-GUN DELIVERY OF HIV-1 DNA FOLLOWED BY RECOMBINANT SUBUNIT PROTEIN BOOSTS

The efficacy of combining immunization with human immunodeficiency vit us type 1 (HIV-1) DNA and HIV-1 recombinant proteins to obtain protect ion from chimeric simian/human immunodeficiency virus (SHIV) was deter mined. Four cynomolgus monkeys received four gene-gun immunizations in traepidermally of plasmid DNA encoding HIV-l LAI env(gp160), gag, tat, nef, and rev proteins. Ten micrograms of DNA was used per immunizatio n. The animals were boosted twice intramuscularly with 50 mu g of HIV- 1LAI Env (MicroGeneSys), Gag, Tat, Nef, and Rev recombinant proteins m ixed in Ribi adjuvant. The antibody responses were amplified following the administration of the recombinant subunit boosts. One month after the final subunit immunization, the vaccinated animals together with four control animals were challenged intravenously with 10 monkey infe ctious doses of SHIV that expresses the env, tar and rev genes of HIV- 1 and gag and nei from SIV. However, only low titers of neutralizing a ntibodies were present at the day of challenge. The consecutive HIV-1 DNA and recombinant protein immunizations induced B- and T-cell respon ses but not protection against SHIV replication nor reduction of the v iral load. (C) 1998 Academic Press