CLADE B-BASED HIV-1 VACCINES ELICIT CROSS-CLADE CYTOTOXIC T-LYMPHOCYTE REACTIVITIES IN UNINFECTED VOLUNTEERS

A fundamental goal of current strategies to develop an efficacious vac cine for AIDS is the elicitation of broadly reactive cytotoxic T lymph ocyte (CTL) reactivities capable of destroying virally infected target s, Recent application of recombinant canarypox ALVAC/HIV-1 vectors as vaccine immunogens in HIV-1, -noninfected volunteers has produced CTL responses in a significant number of vaccinees, Using a newly develope d targeting strategy, we examined the capacity of vaccine-induced CTL to lyse autologous targets infected with a diverse group of viral isol ates. CTL derived from recipients of a canarypox ALVAC/HIV-1 gp160 (MN ) vaccine were found capable of lysing autologous CD4(+) lymphoblasts infected with the prototypic LAI strain of HIV-1. When tested against autologous targets infected with primary HIV-1 isolates representing g enetically diverse vira clades, CTL from ALVAC/gp160 recipients showed both a broad pattern of cytolysis in which viruses from all clades te sted were recognized as well as a highly restricted pattern in which n o primary isolates, including clade B, were lysed, Differences in the HLA haplotypes of the volunteers immunized with the envelope vector mi ght be a major determinant of the relative breadth of their CTL respon se, In contrast to ALVAC/gp160 vaccinees, recipients of the ALVAC/HIV- 1 immunogen containing envelope as well as gag and protease genes cons istently had CTL reactivities effective against a spectrum of primary isolate-infected targets, These studies demonstrate for the first time that clade B-based canarypox vaccines can elicit broad CTL reactiviti es capable of recognizing viruses belonging to genetically diverse HIV -1 clades, The results also reinforce the impact of viral core element s in the vaccine as well as the pattern of major histocompatibility co mplex class I allelic expression by the vaccine recipient in determini ng the relative breadth of the cellular response.