title: Evaluation of aldrithiol-2-inactivated preparations of HIV type 1 subtypes A, B, and D as reagents to monitor T cell responses.
abstract: The development of HIV vaccines is an urgent priority and there is need to generate reagents representing multiple subtypes that can be used to screen HIV-1-specific responses. We used Aldrithiol-2 (AT-2), a mild oxidizing reagent, to eliminate the infectivity of HIV while maintaining its structure and ability to be processed for presentation to T cells. Inactivated subtype A, B, and D viruses were evaluated for their ability to stimulate T cell responses in PBMC samples from 18 U.S. subjects infected with HIV-1 subtype B and 32 Ugandan subjects infected with subtypes A and D or recombinants AC and AD. Five HIV-1-negative samples were also analyzed. T cell responses to AT-2-inactivated viral isolates were monitored by interferon-gamma (IFN-gamma) intracellular cytokine secretion (ICS) analysis; matched microvesicle preparations served as negative controls. Among the 18 subtype B infected subjects, 39% had CD3(+) CD4 (+) IFN-gamma responses and 67% had CD3(+) CD8(+) IFN-gamma responses. Of the 32 Ugandan subjects, 34% demonstrated CD3(+) CD4(+) IFN-gamma responses and 78% demonstrated CD3(+) CD8(+) IFN-gamma responses. Both subtype-specific and cross-reactive responses were observed. Responses to the AT-2 viruses tended to be lower in magnitude than those detected by a set of overlapping gag peptides. Robust lymphoproliferative responses to AT-2 viruses were seen in a subset of subjects. In conclusion, AT-2-inactivated HIV-1 virions stimulated both CD4 and CD8 HIV-1-specific responses and may provide an additional reagent for screening HIV-1-specific responses in HIV seropositives and vaccinees.
authors.affiliation: U.S. Military HIV Research Program/Henry Jackson Foundation, 13 Taft Court, Rockville, MD 20850, USA.
authors.forename: A
authors.initials: A
authors.lastname: Rutebemberwa
authors.forename: J W
authors.initials: JW
authors.lastname: Bess
authors.forename: B
authors.initials: B
authors.lastname: Brown
authors.forename: M
authors.initials: M
authors.lastname: Arroyo
authors.forename: M
authors.initials: M
authors.lastname: Eller
authors.forename: B
authors.initials: B
authors.lastname: Slike
authors.forename: V
authors.initials: V
authors.lastname: Polonis
authors.forename: F
authors.initials: F
authors.lastname: McCutchan
authors.forename: J R
authors.initials: JR
authors.lastname: Currier
authors.forename: D
authors.initials: D
authors.lastname: Birx
authors.forename: M
authors.initials: M
authors.lastname: Robb
authors.forename: M
authors.initials: M
authors.lastname: Marovich
authors.forename: J D
authors.initials: JD
authors.lastname: Lifson
authors.forename: J H
authors.initials: JH
authors.lastname: Cox
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives / Q000494:pharmacology; D016915:AIDS Vaccines; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002478:Cells, Cultured; D004220:Disulfides / Q000494:pharmacology; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D038301:Virus Inactivation
chemical_list: D016915:AIDS Vaccines; D004220:Disulfides; D016877:Oxidants; C001105:2,2'-dipyridyl disulfide; D015082:2,2'-Dipyridyl; D007371:Interferon-gamma