Short Communication: Small-Molecule CD4 Mimetics Sensitize HIV-1-Infected Cells to Antibody-Dependent Cellular Cytotoxicity by Antibodies Elicited by Multiple Envelope Glycoprotein Immunogens in Nonhuman Primates.

Published

Journal Article

Recent studies have linked antibody Fc-mediated effector functions with control of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus infections. Interestingly, the presence of antibodies with potent antibody-dependent cellular cytotoxicity (ADCC) activity in RV144 vaccine trial participants correlated inversely with HIV-1 acquisition risk. These antibodies were recently found to recognize epitopes on the HIV-1 envelope (Env) glycoprotein exposed upon Env-CD4 binding. Accordingly, small-molecule CD4 mimetics (CD4mc) that induce Env to sample the CD4-bound conformation were shown to sensitize HIV-1-infected cells to ADCC mediated by sera from HIV-1-infected individuals. However, it remains unknown whether antibodies elicited through immunization can also mediate CD4mc-induced ADCC. In this study, we tested the capacity of CD4mc to sensitize HIV-1-infected cells to ADCC by sera from Env-vaccinated nonhuman primates using a FACS-based ADCC assay. In parallel, we evaluated the ability of CD4mc to sensitize HIV-1 viral particles to neutralization by sera from these immunized animals. We found that the vaccine-induced antibodies were able to mediate ADCC and viral neutralization in the presence, but not the absence, of CD4mc. Thus, CD4mc are capable of sensitizing HIV-1-infected cells to ADCC and infectious viral particles to neutralization by easy-to-elicit antibodies that are otherwise unable to mediate these activities.

Full Text

Duke Authors

Cited Authors

  • Ding, S; Verly, MM; Princiotto, A; Melillo, B; Moody, AM; Bradley, T; Easterhoff, D; Roger, M; Hahn, BH; Madani, N; Smith, AB; Haynes, BF; Sodroski, J; Finzi, A

Published Date

  • May 2017

Published In

Volume / Issue

  • 33 / 5

Start / End Page

  • 428 - 431

PubMed ID

  • 27846736

Pubmed Central ID

  • 27846736

Electronic International Standard Serial Number (EISSN)

  • 1931-8405

International Standard Serial Number (ISSN)

  • 0889-2229

Digital Object Identifier (DOI)

  • 10.1089/aid.2016.0246

Language

  • eng