CROSS-CLADE-SPECIFIC CYTOTOXIC T-LYMPHOCYTES IN HIV-1-INFECTED CHILDREN

We studied cytotoxic T lymphocyte (CTL) cross-reactivity between human immunodeficiency virus type 1 (HIV-1) subtypes within a group of infa nts infected with either HIV-1 B or non-B clade. Fifteen children were infected with a clade B virus. Nine were infected with non-B virus, i ncluding two clade A, four clade D, two clade F, and one clade G. CTL activities from in vitro activated peripheral blood mononuclear cells were tested against autologous cell line infected with recombinant vac cinia viruses encoding for Env, Gag, Pol, or Nef proteins from a clade A or B isolate. HIV-I-specific CTL elicited from infection with clade B virus could lyse targets expressing clade A proteins, and vice vers a. In infants with positive CTL responses, cross-clade recognition was predominant and was detected within 88% of the Pol, 83% of the Nef, 6 7% of the Gag, and 55% of the Env responders. Longitudinal studies sho wed that CTL cross-reactivity to both B and A targets was stable for s everal years. Elicitation of CTL reactivities capable of elimination o f virus-infected cells is an important goal for the development of an efficient AIDS vaccine. The significant cross-reactivity of CTL shown in this study supports the concept that vaccines developed using a sin gle-clade immunogen may be applicable to induce broadly reactive T cel l responses. (C) 1998 Academic Press