Protection from immunodeficiency virus challenges in rhesus macaques by multicomponent DNA immunization

Multicomponent DNA vaccines were used to elicit immune responses, which can impact viral challenge in three separate rhesus macaque models. Eight rhes us macaques were immunized with DNA vaccines for HIV env/rev and SIV gag/po l and were challenged intravenously with 10 animal infective doses (AID(50) ) of cell-free SHIV IIIB. Three of eight immunized rhesus macaques were pro tected, exhibiting no detectable virus. Animals protected from nonpathogeni c SHIVIIIB challenge were rested for extended periods of time and were rech allenged first with pathogenic SIVmac239 and subsequently with pathogenic S HIV89.6P viruses. Following the pathogenic challenges, all three vaccinated animals were negative for viral coculture and antigenemia and were negativ e by PCR. In contrast, the control animals exhibited antigenemia by 2 weeks postchallenge and exhibited greater than 10 logs of virus/10(6) cells in l imiting dilution coculture. The control animals exhibited CD4 cell loss and developed SIV-related wasting with high viral burden and subsequently fail ed to thrive. Vaccinated animals remained virus-negative and were protected from the viral load, CD4 loss, disease, and death. We observed strong Th1- type cellular immune responses in the protected macaques throughout the stu dy, suggesting their important roles in protection. These studies support t he finding that multicomponent DNA vaccines can directly impact viral repli cation and disease in a highly pathogenic challenge system, thus potentiall y broadening our strategies against HIV. (C) 2001 Academic Press.