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Immune checkpoint modulation enhances HIV-1 antibody induction.

Publication ,  Journal Article
Bradley, T; Kuraoka, M; Yeh, C-H; Tian, M; Chen, H; Cain, DW; Chen, X; Cheng, C; Ellebedy, AH; Parks, R; Barr, M; Sutherland, LL; Scearce, RM ...
Published in: Nat Commun
February 19, 2020

Eliciting protective titers of HIV-1 broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development, but current vaccine strategies have yet to induce bnAbs in humans. Many bnAbs isolated from HIV-1-infected individuals are encoded by immunoglobulin gene rearrangments with infrequent naive B cell precursors and with unusual genetic features that may be subject to host regulatory control. Here, we administer antibodies targeting immune cell regulatory receptors CTLA-4, PD-1 or OX40 along with HIV envelope (Env) vaccines to rhesus macaques and bnAb immunoglobulin knock-in (KI) mice expressing diverse precursors of CD4 binding site HIV-1 bnAbs. CTLA-4 blockade augments HIV-1 Env antibody responses in macaques, and in a bnAb-precursor mouse model, CTLA-4 blocking or OX40 agonist antibodies increase germinal center B and T follicular helper cells and plasma neutralizing antibodies. Thus, modulation of CTLA-4 or OX40 immune checkpoints during vaccination can promote germinal center activity and enhance HIV-1 Env antibody responses.

Duke Scholars

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

February 19, 2020

Volume

11

Issue

1

Start / End Page

948

Location

England

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Vaccination
  • Transcriptome
  • T-Lymphocytes, Helper-Inducer
  • Receptors, OX40
  • Mice, Transgenic
  • Mice
  • Macaca mulatta
  • Lymphocyte Activation
  • Immunologic Factors
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Bradley, T., Kuraoka, M., Yeh, C.-H., Tian, M., Chen, H., Cain, D. W., … Haynes, B. F. (2020). Immune checkpoint modulation enhances HIV-1 antibody induction. Nat Commun, 11(1), 948. https://doi.org/10.1038/s41467-020-14670-w

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

February 19, 2020

Volume

11

Issue

1

Start / End Page

948

Location

England

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Vaccination
  • Transcriptome
  • T-Lymphocytes, Helper-Inducer
  • Receptors, OX40
  • Mice, Transgenic
  • Mice
  • Macaca mulatta
  • Lymphocyte Activation
  • Immunologic Factors