Antibody-dependent cellular cytotoxicity-competent antibodies against HIV-1-infected cells in plasma from HIV-infected subjects

Franck P. Dupuy, Sanket Kant, Alexandre Barbé, Jean Pierre Routy, Julie Bruneau, Bertrand Lebouché, Cécile Tremblay, Marzena Pazgier, Andrés Finzi, Nicole F. Bernard*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Measuring Envelope (Env)-specific antibody (Ab)-dependent cellular cytotoxicity (ADCC)-competent Abs in HIV plasma is challenging because Env displays distinctive epitopes when present in a native closed trimeric conformation on infected cells or in a CD4-bound conformation on uninfected bystander cells. We developed an ADCC model which distinguishes Env-specific ADCC-competent Abs based on their capacity to eliminate infected, bystander, or Env rgp120-coated cells as a surrogate for shed gp120 on bystander cells. A panel of monoclonal Abs (MAbs), used to opsonize these target cells, showed that infected cells were preferentially recognized/eliminated by MAbs to CD4 binding site, V3 loop, and viral spike epitopes whereas bystander/coated cells were preferentially recognized/eliminated by Abs to CD4-induced (CD4i) epitopes. In HIV-positive (HIV) plasma, Env-specific Abs recognized and supported ADCC of infected cells, though a majority were directed toward CD4i epitopes on bystander cells. For ADCC activity to be effective in HIV control, ADCC-competent Abs need to target genuinely infected cells. IMPORTANCE HIV Env-specific nonneutralizing Abs (NnAbs) able to mediate ADCC have been implicated in protection from HIV infection. However, Env-specific NnAbs have the capacity to support ADCC of both HIV-infected and HIV-uninfected bystander cells, potentially leading to misinterpretations when the assay used to measure ADCC does not distinguish between the two target cell types present in HIV cultures. Using a novel ADCC assay, which simultaneously quantifies the killing activity of Env-specific Abs on both infected and uninfected bystander cells, we observed that only a minority of Env-specific Abs in HIV plasma mediated ADCC of genuinely HIV-infected cells displaying Env in its native closed conformation. This assay can be used for the development of vaccine strategies aimed at eliciting Env-specific Ab responses capable of controlling HIV infection.

Original languageEnglish
Article numbere02690-19
Issue number6
StatePublished - 1 Nov 2019
Externally publishedYes


  • ADCC
  • ADCC assay
  • Broadly neutralizing antibodies
  • CD4 binding site antibodies
  • CD4i antibodies
  • HIV Envelope
  • Neutralizing antibodies


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