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: Guido Ferrari, Wesley Neal, Janet Ottinger, Anizsa M Jones, Bradley H Edwards, Paul Goepfert, Michael R Betts, Richard A Koup, Susan Buchbinder, M Juliana McElrath, Jim Tartaglia, Kent J Weinhold
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 173 Issue 3 Pg. 2126-33 (Aug 01 2004) ISSN: 0022-1767 [Print] United States
• PMID: 15265949 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• AIDS Vaccines
• Epitopes, T-Lymphocyte
• Gene Products, gag
• HIV Antigens
• HLA-A Antigens
• HLA-A*02:01 antigen
• HLA-A2 Antigen
• Immunodominant Epitopes
• Peptide Fragments
• Vaccines, DNA
• Vaccines, Synthetic
• env Gene Products, Human Immunodeficiency Virus
• p17 gag peptide, human immunodeficiency virus

Topics

• AIDS Vaccines (immunology)
• Alleles
• Canarypox virus (immunology)
• Epitopes, T-Lymphocyte (immunology)
• Gene Products, gag (chemistry, immunology)
• HIV Antigens (immunology)
• HIV Infections (blood, immunology)
• HIV Seronegativity (immunology)
• HIV-1 (immunology)
• HLA-A Antigens (genetics, immunology)
• HLA-A2 Antigen
• Humans
• Immunization, Secondary
• Immunodominant Epitopes (immunology)
• Peptide Fragments (immunology)
• T-Cell Antigen Receptor Specificity
• T-Lymphocytes, Cytotoxic (immunology)
• Vaccination
• Vaccines, DNA (immunology)
• Vaccines, Synthetic (immunology)
• env Gene Products, Human Immunodeficiency Virus