Clade B-based HIV-1 vaccines elicit cross-clade cytotoxic T lymphocyte reactivities in uninfected volunteers.

Journal Article (Journal Article)

A fundamental goal of current strategies to develop an efficacious vaccine for AIDS is the elicitation of broadly reactive cytotoxic T lymphocyte (CTL) reactivities capable of destroying virally infected targets. 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 developed targeting strategy, we examined the capacity of vaccine-induced CTL to lyse autologous targets infected with a diverse group of viral isolates. 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 genetically diverse viral clades, CTL from ALVAC/gp160 recipients showed both a broad pattern of cytolysis in which viruses from all clades tested were recognized as well as a highly restricted pattern in which no primary isolates, including clade B, were lysed. Differences in the HLA haplotypes of the volunteers immunized with the envelope vector might be a major determinant of the relative breadth of their CTL response. In contrast to ALVAC/gp160 vaccinees, recipients of the ALVAC/HIV-1 immunogen containing envelope as well as gag and protease genes consistently 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 reactivities capable of recognizing viruses belonging to genetically diverse HIV-1 clades. The results also reinforce the impact of viral core elements in the vaccine as well as the pattern of major histocompatibility complex class I allelic expression by the vaccine recipient in determining the relative breadth of the cellular response.

Full Text

Duke Authors

Cited Authors

  • Ferrari, G; Humphrey, W; McElrath, MJ; Excler, JL; Duliege, AM; Clements, ML; Corey, LC; Bolognesi, DP; Weinhold, KJ

Published Date

  • February 18, 1997

Published In

Volume / Issue

  • 94 / 4

Start / End Page

  • 1396 - 1401

PubMed ID

  • 9037064

Pubmed Central ID

  • PMC19802

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.94.4.1396


  • eng

Conference Location

  • United States