IMMUNIZATION WITH SUBUNIT HUMAN-IMMUNODEFICIENCY-VIRUS VACCINE GENERATES STRONGER T-HELPER CELL-IMMUNITY THAN NATURAL INFECTION

Healthy, human immunodeficiency virus seronegative (HIV-) volunteers were multiply immunized with a recombinant gp 160 (rgp160) candidate acquired immunodeficiency syndrome (AIDS) vaccine. Peripheral blood lymphocytes from volunteers immunized with 40-mu-g or with 80-mu-g (two volunteers per group) of rgp160, as well as from control donors, were tested for T helper (T(h)) cell function either prior to immunization, 8 to 12 months after the third immunization, or 2 to 5 months after the fourth immunization. The T(h) cell functional tests included antigen-induced in vitro interleukin 2 (IL2) production and proliferation in response to influenza A virus (FLU) and to four synthetic peptides of HIV gp120 and gp160, previously demonstrated to be recognized by T cells from HIV naturally infected patients. Our results demonstrate the following: (a) immunization of HIV- individuals with rgp160 results in IL2 production and T cell proliferation in response to HIV determinants; (b) boosting with rgp160 enhances T(h) function; (c) HIV-specific T(h) function is up to 100-fold greater in the multiply immunized volunteers than that observed in asymptomatic, HIV-infected individuals; and (d) multiple immunization with rgp160 does not impair T(h) function to a non-HIV antigen such as influenza A virus. These results indicate that immunization of uninfected individuals with an HIV subunit vaccine results in much stronger T(h) cell immunity than does natural infection and suggests that vaccination against HIV may be possible.