title: Absence of immunodominant anti-Gag p17 (SL9) responses among Gag CTL-positive, HIV-uninfected vaccine recipients expressing the HLA-A*0201 allele.
abstract: According to a number of previous reports, control of HIV replication in humans appears to be linked to the presence of anti-HIV-1 Gag-specific CD8 responses. During the chronic phase of HIV-1 infection, up to 75% of the HIV-infected individuals who express the histocompatibility leukocyte Ag (HLA)-A*0201 recognize the Gag p17 SLYNTVATL (aa residues 77-85) epitope (SL9). However, the role of the anti-SL9 CD8 CTL in controlling HIV-1 infection remains controversial. In this study we determined whether the pattern of SL9 immunodominance in uninfected, HLA-A*0201 HIV vaccine recipients is similar to that seen in chronically HIV-infected subjects. The presence of anti-SL9 responses was determined using a panel of highly sensitive cellular immunoassays, including peptide:MHC tetramer binding, IFN-gamma ELISPOT, and cytokine flow cytometry. Thirteen HLA-A*0201 vaccinees with documented anti-Gag CD8 CTL reactivities were tested, and none had a detectable anti-SL9 response. These findings strongly suggest that the pattern of SL9 epitope immunodominance previously reported among chronically infected, HLA-A*0201-positive patients is not recapitulated in noninfected recipients of Gag-containing canarypox-based candidate vaccines and may be influenced by the relative immunogenicity of these constructs.
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA. gflmp@duke.edu
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.forename: Wesley
authors.initials: W
authors.lastname: Neal
authors.forename: Janet
authors.initials: J
authors.lastname: Ottinger
authors.forename: Anizsa M
authors.initials: AM
authors.lastname: Jones
authors.forename: Bradley H
authors.initials: BH
authors.lastname: Edwards
authors.forename: Paul
authors.initials: P
authors.lastname: Goepfert
authors.forename: Michael R
authors.initials: MR
authors.lastname: Betts
authors.forename: Richard A
authors.initials: RA
authors.lastname: Koup
authors.forename: Susan
authors.initials: S
authors.lastname: Buchbinder
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.forename: Jim
authors.initials: J
authors.lastname: Tartaglia
authors.forename: Kent J
authors.initials: KJ
authors.lastname: Weinhold
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000483:Alleles; D028121:Canarypox virus / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015683:Gene Products, gag / Q000737:chemistry / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D015658:HIV Infections / Q000097:blood / Q000276:immunology; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology*; D015789:HLA-A2 Antigen; D006801:Humans; D007117:Immunization, Secondary; D016056:Immunodominant Epitopes / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015488:HIV Antigens; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus; C473991:p17 gag peptide, human immunodeficiency virus