title: Selection of human anti-HIV broadly neutralizing antibodies occurs within the context of frozen 1F7-idiotypic repertoire.
abstract: OBJECTIVE
  Most HIV-infected individuals develop HIV-specific antibodies (Abs) exhibiting a common idiotype designated as 1F7. Expression of this idiotype establishes idiotypic-driven repertoire freeze, maintaining antibody responses ineffective at controlling autologous contemporaneous viruses. As such, this study investigated the temporal dynamics of 1F7-idiotype expression, as well as the role of this idiotype in the selection of HIV-specific broadly neutralizing antibodies (BnAbs).
  
  
  METHODS
  This study investigated the timing of appearance and persistence of 1F7-idiotypic HIV-specific Abs by screening plasma samples from individuals followed longitudinally starting in primary HIV infection. The expression of 1F7 on HIV-specific BnAbs was also investigated to determine whether their development occurs within the context of 1F7-idiotypic repertoire freeze.
  
  
  METHODS
  The 1F7 idiotype was detected on gp120, gp41 and membrane proximal external region (MPER) peptide-specific Abs using an enzyme-linked immunosorbent assay (ELISA). HIV-specific Abs in longitudinal plasma samples from six patients and six BnAbs were tested for the presence of the 1F7 idiotype.
  
  
  RESULTS
  The idiotype was expressed on HIV-specific Abs within 3 months of infection, with the magnitude of 1F7 detection increasing with time from infection. The 1F7 idiotype was also expressed on all BnAbs tested.
  
  
  CONCLUSIONS
  These results demonstrate that HIV-specific antibody responses are restricted within the 1F7 idiotype from early infection onwards, and that six well characterized BnAbs developed within the context of 1F7-idiotypic repertoire freeze. Future research should evaluate the necessity of the 1F7 idiotype for broad neutralization, and determine if vaccines should target Abs within or outside this idiotypic space.
authors.affiliation: Research Institute of the McGill University Health Centre, Canada.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Parsons
authors.forename: Danielle
authors.initials: D
authors.lastname: Rouleau
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Routy
authors.forename: Roger
authors.initials: R
authors.lastname: LeBlanc
authors.forename: Michael D
authors.initials: MD
authors.lastname: Grant
authors.forename: Nicole F
authors.initials: NF
authors.lastname: Bernard
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D008297:Male; D008875:Middle Aged
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D007130:Immunoglobulin Idiotypes