Vijaya Madhavi1, Archana Kulkarni, Ashwini Shete, Wen S Lee, Milla R Mclean, Anne B Kristensen, Manisha Ghate, Bruce D Wines, Phillip M Hogarth, Matthew S Parsons, Anthony Kelleher, David A Cooper, Janaki Amin, Sean Emery, Madhuri Thakar, Stephen J Kent. 1. *Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, Australia; †Department of Immunology and Serology, National AIDS Research Institute, Pune, India; ‡Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia; §Department of Immunology, Monash University Central Clinical School, Melbourne, Victoria, Australia; ‖Department of Pathology, the University of Melbourne, Melbourne, Victoria, Australia; ¶Kirby Institute, University of New South Wales, Sydney, Australia; #St Vincent's Centre for Applied Medical Research, Darlinghurst, New South Wales, Australia; **Melbourne Sexual Health Clinic and Infectious Diseases Department, Alfred Hospital, Central Clinical School, Monash University, Carlton, Victoria, Australia; and ††ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, the University of Melbourne, Melbourne, Australia.
Abstract
BACKGROUND: There is growing interest in immune therapies to clear the latent HIV-1 after combination antiretroviral therapy (cART). There is limited information on the effect of cART on antibody-dependent cellular cytotoxicity (ADCC), and no studies have directly compared ADCC in HIV-1 subtype B- and subtype C-infected subjects. The effect of improving immunocompetence on ADCC to influenza also remains unexplored. METHODS: The effect of cART on HIV-1- and influenza-specific ADCC was analyzed in 2 cohorts (39 subtype B- and 47 subtype C-infected subjects) before and after 2 years of cART. ADCC analyses included an enzyme-linked immunosorbent assay-based dimeric recombinant soluble (rs) FcγRIIIa-binding assay, antibody-dependent natural killer cell activation assay, and ADCC-mediated killing assays. RESULTS: HIV-1 subtype B and C Env-specific antibody binding to dimeric rsFcγRIIIa were reduced in subtypes B- and C-infected cohorts after 2 years of cART (both P < 0.05). Reduced ADCC-mediated killing of target cells expressing subtype B Env in the subtype B-infected cohort (P = 0.003) was observed after 96 weeks of cART, but not of subtype C Env in the subtype C-infected cohort. A greater reduction in ADCC was detected in subjects with baseline CD4 counts >300 cells/μL (P < 0.05). The resolving immunodeficiency after 96 weeks of cART resulted in improved HA-specific ADCC to 6 strains of influenza (all P < 0.01). CONCLUSIONS: cART results in HIV-1 antigen loss and reductions in HIV-1 Env-specific antibodies with Fc functionality in both subtype B- and C-infected subjects, particularly in immunocompetent subjects. Simultaneously, cART improves ADCC to diverse strains of influenza, suggesting reduction in influenza disease after cART.
BACKGROUND: There is growing interest in immune therapies to clear the latent HIV-1 after combination antiretroviral therapy (cART). There is limited information on the effect of cART on antibody-dependent cellular cytotoxicity (ADCC), and no studies have directly compared ADCC in HIV-1 subtype B- and subtype C-infected subjects. The effect of improving immunocompetence on ADCC to influenza also remains unexplored. METHODS: The effect of cART on HIV-1- and influenza-specific ADCC was analyzed in 2 cohorts (39 subtype B- and 47 subtype C-infected subjects) before and after 2 years of cART. ADCC analyses included an enzyme-linked immunosorbent assay-based dimeric recombinant soluble (rs) FcγRIIIa-binding assay, antibody-dependent natural killer cell activation assay, and ADCC-mediated killing assays. RESULTS:HIV-1 subtype B and C Env-specific antibody binding to dimeric rsFcγRIIIa were reduced in subtypes B- and C-infected cohorts after 2 years of cART (both P < 0.05). Reduced ADCC-mediated killing of target cells expressing subtype B Env in the subtype B-infected cohort (P = 0.003) was observed after 96 weeks of cART, but not of subtype C Env in the subtype C-infected cohort. A greater reduction in ADCC was detected in subjects with baseline CD4 counts >300 cells/μL (P < 0.05). The resolving immunodeficiency after 96 weeks of cART resulted in improved HA-specific ADCC to 6 strains of influenza (all P < 0.01). CONCLUSIONS: cART results in HIV-1 antigen loss and reductions in HIV-1Env-specific antibodies with Fc functionality in both subtype B- and C-infected subjects, particularly in immunocompetent subjects. Simultaneously, cART improves ADCC to diverse strains of influenza, suggesting reduction in influenza disease after cART.
Authors: Wen Shi Lee; Anne B Kristensen; Thomas A Rasmussen; Martin Tolstrup; Lars Østergaard; Ole S Søgaard; Bruce D Wines; P Mark Hogarth; Arnold Reynaldi; Miles P Davenport; Sean Emery; Janaki Amin; David A Cooper; Virginia L Kan; Julie Fox; Henning Gruell; Matthew S Parsons; Stephen J Kent Journal: J Virol Date: 2017-07-12 Impact factor: 5.103
Authors: Sai Priya Anand; Jérémie Prévost; Sophie Baril; Jonathan Richard; Halima Medjahed; Jean-Philippe Chapleau; William D Tolbert; Sharon Kirk; Amos B Smith; Bruce D Wines; Stephen J Kent; P Mark Hogarth; Matthew S Parsons; Marzena Pazgier; Andrés Finzi Journal: J Virol Date: 2019-01-17 Impact factor: 5.103
Authors: Prossy Naluyima; Kerri G Lal; Margaret C Costanzo; Gustavo H Kijak; Veronica D Gonzalez; Kim Blom; Leigh Anne Eller; Matthew Creegan; Ting Hong; Dohoon Kim; Thomas C Quinn; Niklas K Björkström; Hans-Gustaf Ljunggren; David Serwadda; Elly T Katabira; Nelson K Sewankambo; Ronald H Gray; Jared M Baeten; Nelson L Michael; Fred Wabwire-Mangen; Merlin L Robb; Diane L Bolton; Johan K Sandberg; Michael A Eller Journal: J Immunol Date: 2019-09-13 Impact factor: 5.422
Authors: B D Wines; C W Tan; E Duncan; S McRae; R I Baker; R K Andrews; S Esparon; E E Gardiner; P M Hogarth Journal: J Thromb Haemost Date: 2018-11-20 Impact factor: 5.824
Authors: Hugh Billings; Bruce D Wines; Wayne B Dyer; Robert J Center; Halina M Trist; Stephen J Kent; P Mark Hogarth Journal: AIDS Res Hum Retroviruses Date: 2019-08-21 Impact factor: 2.205