title: Vaccine-delivered HIV envelope inhibits CD4(+) T-cell activation, a mechanism for poor HIV vaccine responses.
abstract: The human immunodeficiency virus (HIV) causes impairment of the immune system in part by targeting CD4(+) T cells for infection and dysfunction. HIV envelope (Env) present on free virions and infected cells causes dysfunction of uninfected bystander CD4(+) T cells via interaction with both CD4 and coreceptors. Env is commonly used as part of a cocktail of HIV antigens in current vaccines. In DNA and viral vector vaccine approaches, antigen-presenting cells (APCs) and non-APCs in the vicinity of the vaccine delivery site and draining lymph node express vaccine-derived antigens. The studies here demonstrate that cell-surface expression of Env on APCs and non-APCs as part of the vaccine action causes an inhibition of antigen-induced CD4(+) T-cell activation and proliferation mediated by CD4 binding and suggests a potential mechanism for reduced activity of Env-containing HIV vaccines. Similar studies using a functional Env lacking CD4 binding circumvented suppression, suggesting an alternative and potentially superior approach to HIV vaccine design.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Kathy
authors.initials: K
authors.lastname: Fernando
authors.forename: Haitao
authors.initials: H
authors.lastname: Hu
authors.forename: Houping
authors.initials: H
authors.lastname: Ni
authors.forename: James A
authors.initials: JA
authors.lastname: Hoxie
authors.forename: Drew
authors.initials: D
authors.lastname: Weissman
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology; D015415:Biomarkers; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015854:Up-Regulation; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000941:Antigens; D015415:Biomarkers; D017252:CD3 Complex; D015704:CD4 Antigens; D007376:Interleukin-2; D050799:STAT5 Transcription Factor; D014759:Viral Envelope Proteins; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases