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 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.
Ferrari
G
G
Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Humphrey
W
W
McElrath
M J
MJ
Excler
J L
JL
Duliege
A M
AM
Clements
M L
ML
Corey
L C
LC
Bolognesi
D P
DP
Weinhold
K J
KJ
D016915:AIDS Vaccines / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000145:classification / Q000276:immunology*; D006801:Humans; D016131:Lymphocyte Subsets; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics
D016915:AIDS Vaccines; D019302:HIV Envelope Protein gp160; D014614:Vaccines, Synthetic