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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.

Publication ,  Journal Article
Ding, S; Verly, MM; Princiotto, A; Melillo, B; Moody, AM; Bradley, T; Easterhoff, D; Roger, M; Hahn, BH; Madani, N; Smith, AB; Haynes, BF ...
Published in: AIDS Res Hum Retroviruses
May 2017

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.

Duke Scholars

Published In

AIDS Res Hum Retroviruses

DOI

EISSN

1931-8405

Publication Date

May 2017

Volume

33

Issue

5

Start / End Page

428 / 431

Location

United States

Related Subject Headings

  • Virology
  • Macaca mulatta
  • HIV-1
  • HIV Antibodies
  • Flow Cytometry
  • CD4-Positive T-Lymphocytes
  • CD4 Antigens
  • Biomimetics
  • Antibody-Dependent Cell Cytotoxicity
  • Animals
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ding, S., Verly, M. M., Princiotto, A., Melillo, B., Moody, A. M., Bradley, T., … Finzi, A. (2017). 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. AIDS Res Hum Retroviruses, 33(5), 428–431. https://doi.org/10.1089/AID.2016.0246
Ding, Shilei, Myriam M. Verly, Amy Princiotto, Bruno Melillo, Anthony M. Moody, Todd Bradley, David Easterhoff, et al. “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.AIDS Res Hum Retroviruses 33, no. 5 (May 2017): 428–31. https://doi.org/10.1089/AID.2016.0246.
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. 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. AIDS Res Hum Retroviruses. 2017 May;33(5):428–431.
Journal cover image

Published In

AIDS Res Hum Retroviruses

DOI

EISSN

1931-8405

Publication Date

May 2017

Volume

33

Issue

5

Start / End Page

428 / 431

Location

United States

Related Subject Headings

  • Virology
  • Macaca mulatta
  • HIV-1
  • HIV Antibodies
  • Flow Cytometry
  • CD4-Positive T-Lymphocytes
  • CD4 Antigens
  • Biomimetics
  • Antibody-Dependent Cell Cytotoxicity
  • Animals