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238 Analysis of Clinical Cellular Immune Response following Immunization with an HIV-1 DNA Vaccine
J. D. Boyer*1, C. Kang1, M. Lee1, K. Lacy1, J. Eldridge2, Z. Israel2, R. S. Ginsberg2, R. R. MacGregor1, and D. B. Weiner1
1Univ. of Pennsylvania Sch. of Med., Hosp. of the Univ. of Pennsylvania, Philadelphia, USA and 2Lederle Vaccine Inc., Pearl River, NY, USA
There is a pressing need for an effective vaccine against human immunodeficiency virus (HIV) type 1. DNA vaccines have demonstrated promise in primate studies as well as in Phase I human clinical studies. In this regard, we have immunized 167 individuals with first generation vaccines. The constructs encoded HIV env/rev and HIV-1 gag/pol. The vaccines were administered at increasing doses and have demonstrated safety at cumulative doses as high as 12 mg. In addition, these DNA vaccines induced antigen-specific lymphocyte proliferative responses and antigen-specific production of both interferon-gamma and beta-chemokines. Furthermore, HIV-1-specific Th1-type responses utilizing the more sensitive ELISPOT assay demonstrated the CD4 responses and the number of IFN-gamma producing lymphocytes was dose dependent. For example, 4 of 6 study subjects in a 1-mg HIV-1 env/rev dose group demonstrated the production of IFN-gamma following in vitro stimulation with the envelope or rev HIV-1 proteins. Whereas in the prophylactic setting CD8 responses were observed in only a few individuals, DNA vaccines demonstrated a significant impact on the HIV-1 antigen-specific CD8 cellular immune response in a therapeutic setting. CD8 MHC class I-restricted responses to env, gag, and RT demonstrated 8/13 vaccinees responded versus 0/2 controls. Data will be presented detailing the CD4 and CD8 HIV-1 DNA vaccine-induced cellular immune responses of several clinical studies. Indeed, the immune responses observed in the human clinical studies were not as robust as originally hoped. Yet, the primate studies have demonstrated that low level immune responses induced by SIV DNA-based vaccines are able to suppress SIV viral replication following SIV challenge of Rhesus macaques. Ultimately, suppressing viral replication resulting in a lower viral set point could have a significant impact on disease progression in human patients and potentially impact transmission rates.
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