Evaluation of Aldrithiol-2-inactivated preparations of HIV type 1 subtypes A, B, and D as reagents to monitor T cell responses
AIDS Research and Human Retroviruses
US Military HIV Research Program, Henry Jackson Foundation, Rockville, MD 20850, United States; SAIC Frederick, National Cancer Institute at Frederick, AIDS Vaccine Program, Frederick, MD 21702, United States; Makerere University, Walter Reed Project, Kampala, Uganda; U.S. Military HIV Research Program, Henry Jackson Foundation, 13 Taft Court, Rockville, MD 20850, United States
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-γ) intracellular cytokine secretion (ICS) analysis; matched microvesicle preparations served as negative controls. Among the 18 subtype B infected subjects, 39% had CD3 +CD4+ IFN-γ responses and 67% had CD3 +CD8+ IFN-γ responses. Of the 32 Ugandan subjects, 34% demonstrated CD3+CD4+ IFN-γ responses and 78% demonstrated CD3+CD8+ IFN-γ 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. © Mary Ann Liebert, Inc.
aldrithiol 2; CD3 antigen; CD4 antigen; CD8 antigen; gamma interferon; Human immunodeficiency virus vaccine; inactivated virus vaccine; peptide; unclassified drug; adult; article; CD4+ T lymphocyte; controlled study; cytokine release; drug synthesis; human; Human immunodeficiency virus 1; Human immunodeficiency virus infection; lymphocyte proliferation; nonhuman; nucleotide sequence; priority journal; T lymphocyte; T lymphocyte activation; Uganda; virus inactivation; virus isolation; 2,2'-Dipyridyl; AIDS Vaccines; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cells, Cultured; Disulfides; HIV-1; Humans; Interferon Type II; Oxidants; Virus Inactivation