Elicitation of cluster a and co-receptor binding site antibodies are required to eliminate HIV-1 infected cells

Guillaume Beaudoin-Bussières, Jérémie Prévost, Gabrielle Gendron-Lepage, Bruno Melillo, Junhua Chen, Amos B. Smith, Marzena Pazgier, Andrés Finzi*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

HIV-1-infected individuals raise a polyclonal antibody response targeting multiple envelope glycoprotein (Env) epitopes. Interestingly, two classes of non-neutralizing CD4-induced (CD4i) antibodies, present in the majority of HIV-1-infected individuals have been described to mediate antibody-dependent cellular cytotoxicity (ADCC) in the presence of small CD4 mimetic compounds (CD4mc). These antibodies recognize the coreceptor binding site (CoRBS) and the constant region one and two (C1C2 or inner domain cluster A) of the gp120. In combination with CD4mc they have been shown to stabilize an antibody-vulnerable Env conformation, known as State 2A. Here we evaluated the importance of these two families of Abs in ADCC responses by immunizing guinea pigs with gp120 immunogens that have been modified to elicit or not these types of antibodies. Underlying the importance of anti-CoRBS and anti-cluster A Abs in stabilizing State 2A, ADCC responses were only observed in the presence of these two types of CD4i antibodies. Altogether, our results suggest that these two families of CD4i antibodies must be taken into account when considering future strategies relying on the use of CD4mc to eliminate HIV-1-infected cells in vivo.

Original languageEnglish
Article number710
JournalMicroorganisms
Volume8
Issue number5
DOIs
StatePublished - May 2020
Externally publishedYes

Keywords

  • ADCC
  • Cluster A
  • Coreceptor binding site
  • Guinea pigs
  • HIV-1
  • Small CD4 mimetics

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