title: Breadth of HIV-1 Env-specific antibody-dependent cellular cytotoxicity: relevance to global HIV vaccine design.
abstract: OBJECTIVE
  The objective of this study is to determine the breadth of HIV-1 Env-specific antibody-dependent cellular cytotoxicity (ADCC) in HIV controllers and HIV progressors with a view to design globally relevant HIV vaccines.
  
  
  METHODS
  The breadth of ADCC towards four major HIV-1 Env subtypes was measured in vitro for 11 HIV controllers and 11 HIV progressors.
  
  
  METHODS
  Plasma from 11 HIV controllers (including long-term slow progressors, viremic controllers, elite controller and posttreatment controller) and 11 HIV progressors, mostly infected with HIV-1 subtype B, was analysed for ADCC responses. ADCC assays were performed against 10 HIV-1 gp120 and 8 gp140 proteins from four major HIV-1 subtypes (A, B, C and E) and 3 glycosylation-mutant gp140 proteins.
  
  
  RESULTS
  ADCC-mediated natural killer cell activation was significantly broader (P = 0.02) and of higher magnitude (P < 0.001) in HIV controllers than in HIV progressors. HIV controllers also showed significantly higher magnitude of ADCC-mediated killing of Env-coated target cells than HIV progressors to both HIV-1 subtype B and the heterologous subtype E gp140 (P = 0.001). We found good ADCC reactivity to subtype B and E Envs, less cross-reactivity to subtype A and minimal cross-reactivity to subtype C Envs. Glycosylation-dependent ADCC epitopes comprise a significant proportion of the total Env-specific ADCC response, as evident from the reduction in ADCC to nonglycosylated form of HIV-1 gp140 (P = 0.004).
  
  
  CONCLUSIONS
  HIV controllers have robust ADCC responses that recognize a broad range of HIV-1 Env. Glycosylation of Env was found to be important for recognition of ADCC epitopes. Identifying conserved ADCC epitopes will assist in designing globally relevant ADCC-based HIV vaccines.
authors.affiliation: aDepartment of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Parkville bMelbourne Sexual Health Clinic, Carlton cInfectious Diseases Unit, Alfred Hospital, Prahran, Victoria, Australia.
authors.forename: Vijaya
authors.initials: V
authors.lastname: Madhavi
authors.forename: Leia H
authors.initials: LH
authors.lastname: Wren
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Center
authors.forename: Christopher
authors.initials: C
authors.lastname: Gonelli
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Winnall
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Parsons
authors.forename: Marit
authors.initials: M
authors.lastname: Kramski
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
authors.forename: Ivan
authors.initials: I
authors.lastname: Stratov
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000328:Adult; D000939:Epitopes / Q000276:immunology; D005260:Female; D005838:Genotype; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D055815:Young Adult; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000939:Epitopes; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus