IMPROVED CELL-MEDIATED IMMUNE-RESPONSES IN HIV-1-INFECTED ASYMPTOMATIC INDIVIDUALS AFTER IMMUNIZATION WITH ENVELOPE GLYCOPROTEIN GP160

Strong specific T-cell responses to human immunodeficiency virus type 1 (HIV-1) gp160 were induced by immunization with recombinant gp160 (r gp160). It was given as postinfection vaccination to 40 asymptomatic H IV-1 seropositive patients. The participants received 6 doses of 160 m u g rgp160 administered intramuscularly at 0, 1, 4, 8, 17, and 26 week s and were monitored for 1 year. Lymphocyte proliferation was performe d by cultivating lymphoid cells in vitro with specific antigens and mi togens. After immunization with gp160, specific T-cell proliferative r esponses were induced in all 40 patients. One week after the sixth imm unization at day 180, a substantially increased response was detected in 98% of the patients, with a mean stimulation index value of 195. Fu rthermore, proliferative responses were also identified, after immuniz ation, against native gp120 and against a peptide representing the V3 region of gp120. In addition to the HIV-specific T-cell responses, inc reased reactivity to several other non-HIV antigens, including tetanus toroid, influenza, measles, and cytomegalovirus, were seen after gp16 0 vaccination. The responses to CMV and measles were interpreted to re present an improved recall antigen response. Such recall antigen respo nses were few in matched HIV-infected controls immunized with influenz a virus only. All patients initially and repeatedly showed a normal ca pacity of total T-cell activation, evaluated by the mitogen phytohemag glutinin (PHA). The trend in CD4 counts improved in 30 of 40 patients during the year of follow-up. The frequency of increases of proliferat ive responses to antigens was associated with a better CD4 trend. Addi tion of zidovudine for 2 weeks after each immunization had no benefici al effects nor did it prevent induction of immune responses. All patie nts tolerated the immunizations well, and no systemic adverse effects were noted. This is a phase I trial, and no definitive conclusions reg arding clinical efficacy can be reached.