HIV type 1-specific inter- and intrasubtype cellular immune responses in HIV type 1-infected Ugandans.
Investigations concerning the extent and nature of subtype-specific and intersubtype immune responses in HIV-1-infected persons are necessary for the development of appropriate candidate vaccines. In the cross-sectional study described here, 26 HIV-1-positive Ugandan patients were tested for their ability to mount HIV antigen-specific cellular immune responses. Subjects were infected with either HIV-1 subtypes A, C, or D. Recombinant vaccinia virus (rVV)-based and peptide-based enzyme-linked immunospot (Elispot) assays were used to evaluate HIV-1-specific gamma-interferon (IFN-gamma) cellular responses. rVV expressing gag, pol, or env proteins derived from HIV-1 subtypes A, B, and D were evaluated for their ability to induce whole HIV-1-protein-specific IFN-gamma responses in 14 patients. A panel of previously identified HLA class I-restricted peptides based on representative sequences from HIV-1 subtypes A, B, C, and D and restricted through HLA-A2, -A29, -B42, -B53, and -B57 alleles were used to evaluate the presence of HIV-1-peptide-specific T cells in 19 patients. Using rVV, 27 of a possible 38 subtype-specific responses (71%) and 56 of a possible 110 intersubtype responses (51%) were observed. When appropriate peptides were used 18 of 39 (46.2%) subtype-specific and 13 of 39 (33.3%) intersubtype responses were observed. Peptide responses were higher quantitatively than those seen when rVV were used. In 7 patients, both rVV and specific peptides were evaluated; in 3 of 7 individuals, global responses were seen despite a lack of measurable HLA-restricted peptide-specific responses demonstrating the need to evaluate a broader range of HIV-specific immune responses.
Henry M. Jackson Foundation, Rockville, Maryland 20850, USA. arutebemberwa@hivresearch.org
Alleluiah
A
Rutebemberwa
Betty
B
Auma
Jill
J
Gilmour
Gareth
G
Jones
David
D
Yirrell
Samantha
S
Rowland
Nesrina
N
Imami
Christine
C
Watera
Pontiano
P
Kaleebu
James
J
Whitworth
Frances
F
Gotch
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005814:Genes, Viral; D015658:HIV Infections / Q000276:immunology; D006679:HIV Seropositivity / Q000276:immunology; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D007111:Immunity, Cellular; D011995:Recombination, Genetic; D014454:Uganda; D014616:Vaccinia virus / Q000235:genetics; D015678:Viral Structural Proteins / Q000235:genetics
D015678:Viral Structural Proteins