title: Moving to human immunodeficiency virus type 1 vaccine efficacy trials: defining T cell responses as potential correlates of immunity.
abstract: There is evidence in both simian immunodeficiency virus and human immunodeficiency virus (HIV) type 1 infection that class I major histocompatibility complex-restricted CD8(+) cytotoxic T lymphocytes play a pivotal role in controlling infection and, potentially, in protecting by immunization. Progress has been made in designing strategies to elicit these responses with HIV-1 vaccines, but methods to reproducibly quantify them have posed difficulties. An interferon-gamma enzyme-linked immunospot assay, using peptide pools spanning the HIV-1 genes, was developed and standardized. This method is rapid (2 days), sensitive (threshold of detection, > or =0.005%), quantitative, feasible using cryopreserved cells, and able to define epitope specificities. When this assay was applied to 36 HIV-1-seropositive and 10 HIV-1-seronegative subjects, it proved to be robust (specificity, 100%). When responses in natural infection were compared with vaccine-induced responses, vaccine recipient responses were > or =1 log lower, which confirms the importance of using this sensitive assay as an initial screen in vaccine protocols.
authors.affiliation: Program in Infectious Diseases, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: Nina D
authors.initials: ND
authors.lastname: Russell
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hudgens
authors.forename: Richard
authors.initials: R
authors.lastname: Ha
authors.forename: Colin
authors.initials: C
authors.lastname: Havenar-Daughton
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002986:Clinical Trials as Topic; D004306:Dose-Response Relationship, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015488:HIV Antigens / Q000737:chemistry / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D013997:Time Factors
chemical_list: D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015488:HIV Antigens; D010455:Peptides; D007371:Interferon-gamma