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Induction of HIV-1-specific T-helper responses and type 1 cytokine secretion following therapeutic vaccination of macaques with a recombinant fowlpoxvirus co-expressing interferon-gamma
Authors:C Jane Dale  Anne  Zhao  Stephen L Jones  David B Boyle  Ian A Ramshaw  & Stephen J Kent
Institution:AIDS Pathogenesis Research Unit, Macfarlane Burnet Centre for Medical Research, Yarra Bend Rd, Fairfield 3078, Victoria, Australia,;Department of Microbiology and Immunology, University of Melbourne, Parkville 3052, Victoria, Australia,;Veterinary Division, CSL Ltd, 45 Poplar Road, Parkville 3052, Victoria, Australia,;CSIRO, Division of Animal Health, Australian Animal Health Laboratories, Geelong 3220, Victoria, Australia,;Division of Cell Biology and Immunology, John Curtin School for Medical Research, Australian National University, Canberra 2601, ACT, Australia
Abstract:Preventive and/or therapeutic vaccines against Human Immunodeficiency Virus (HIV-1) are urgently required. Induction of cellular immunity is favoured since these responses correlate with control of HIV-1. Recombinant fowlpoxvirus (FPV) vaccines encoding both HIV-1 gag/pol and interferon-gamma (FPV gag/pol-IFNΓ) were hypothesised to enhance HIV-specific cellular immunity and were further evaluated in macaques previously infected with HIV-1. A novel assay to detect IFNΓ secretion following HIV antigen stimulation of whole blood was developed to further assess the safety and immunogenicity of the FPV gag/pol-IFNΓ vaccine. Immunisation with FPV gag/pol-IFNΓ safely enhanced HIV-specific IFNΓ secretion following ex vivo stimulation of whole blood, greater than that observed following FPV gag/pol vaccination not co-expressing IFNΓ. Both HIV-specific IFNΓ-spot-forming cells by ELISPOT and CD69 expression by CD4+ lymphocytes were also enhanced following FPV gag/pol-IFNΓ vaccination. Hence, the FPV-HIV vaccine co-expressing IFNΓ stimulated HIV-specific T cell responses in macaques, and should be further evaluated as a therapeutic or preventive HIV vaccine.
Keywords:cellular immunity  ELISOT  CD69  interferon-gamma assay  vaccine vectors
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