Protection from Immunodeficiency Virus Challenges in Rhesus Macaques by Multicomponent DNA Immunization

• Published in: Virology (New York, N.Y.) N.Y.), 2001-07, Vol.285 (2), p.204-217
• Main Authors: Kim, J.Joseph, Yang, Joo-Sung, Nottingham, Liesl K., Lee, Daniel J., Lee, Mark, Manson, Kelledy H., Wyand, Michael S., Boyer, Jean D., Ugen, Kenneth E., Weiner, David B.
• Format: Article
• Language: English
• Subjects: AIDS Vaccines - immunology; Animals; env protein; gag protein; HIV-1 - genetics; HIV-1 - immunology; human immunodeficiency virus; Humans; Macaca mulatta; pol protein; rev protein; Simian Acquired Immunodeficiency Syndrome - prevention & control; simian immunodeficiency virus; Simian Immunodeficiency Virus - immunology; Vaccines, DNA - immunology
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1006/viro.2001.0958

Multicomponent DNA vaccines were used to elicit immune responses, which can impact viral challenge in three separate rhesus macaque models. Eight rhesus macaques were immunized with DNA vaccines for HIV env/rev and SIV gag/pol and were challenged intravenously with 10 animal infective doses (AID50) of cell-free SHIV IIIB. Three of eight immunized rhesus macaques were protected, exhibiting no detectable virus. Animals protected from nonpathogenic SHIVIIIB challenge were rested for extended periods of time and were rechallenged first with pathogenic SIVmac239 and subsequently with pathogenic SHIV89.6P viruses. Following the pathogenic challenges, all three vaccinated animals were negative for viral coculture and antigenemia and were negative by PCR. In contrast, the control animals exhibited antigenemia by 2 weeks postchallenge and exhibited greater than 10 logs of virus/106 cells in limiting dilution coculture. The control animals exhibited CD4 cell loss and developed SIV-related wasting with high viral burden and subsequently failed 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 study, suggesting their important roles in protection. These studies support the finding that multicomponent DNA vaccines can directly impact viral replication and disease in a highly pathogenic challenge system, thus potentially broadening our strategies against HIV.