CELLULAR CYTOTOXIC RESPONSE INDUCED BY DNA VACCINATION IN HIV-1-INFECTED PATIENTS

Background DNA vaccination is known to generate immune responses again st HIV-1 in animal models. We aimed to assess the efficacy of DNA vacc ination in induction of immune responses in HIV-1-infected human being s. Methods Nine symptom-free HIV-1-infected patients were immunised wi th DNA constructs encoding the nef, rev, or tat regulatory genes of HI V-1. The patients were selected for having no or low antibody reactivi ties to these antigens. HIV-1-specific cytotoxic T-lymphocytes (CTLs), precursor frequencies, and antigen-specific proliferative responses w ere measured before, during, and after three immunisations over 6 mont hs. Findings Cellular immune reactivities against the HIV-1 regulatory proteins were absent or low before DNA immunisation. DNA vaccination induced detectable memory cells in all patients and specific cytotoxic ity in eight patients. CTLs were MHC-class-I restricted and mainly of CD8+ origin. In three patients the cellular activity was transient, de creasing after an initial response. Interpretation DNA immunisation wi th HIV-1 genes can induce specific cellular responses in human beings with no apparent side-effects. It is theoretically possible that HIV-1 -specific cytotoxic responses to regulatory proteins could lead to inf ected cells being eliminated before they have released new viral parti cles. However, it is possible that the patients we selected responded less than would nonselected or non-infected individuals. The small num ber of patients presented here does not allow generalisation of our fi ndings.