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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
Published version (DOI) Open Access Copy (Duke) Link to item

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

Chen-Hao Yeh
Author Chen-Hao Yeh Medicine, Duke Human Vaccine Institute
Derek Wilson Cain
Author Derek Wilson Cain Medicine, Duke Human Vaccine Institute
Kevin J Wiehe
Author Kevin J Wiehe Medicine, Duke Human Vaccine Institute
David Charles Montefiori
Author David Charles Montefiori Surgery, Surgical Sciences
Michael Anthony Moody
Author Michael Anthony Moody Pediatrics, Infectious Diseases
Kevin O'Neil Saunders
Author Kevin O'Neil Saunders Surgery, Surgical Sciences
Garnett H. Kelsoe
Author Garnett H. Kelsoe Integrative Immunobiology
Barton Ford Haynes
Author Barton Ford Haynes Medicine, Duke Human Vaccine Institute
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Published In

Nat Commun

DOI

10.1038/s41467-020-14670-w

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
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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
Bradley, Todd, Masayuki Kuraoka, Chen-Hao Yeh, Ming Tian, Huan Chen, Derek W. Cain, Xuejun Chen, et al. “Immune checkpoint modulation enhances HIV-1 antibody induction.” Nat Commun 11, no. 1 (February 19, 2020): 948. https://doi.org/10.1038/s41467-020-14670-w.
Bradley T, Kuraoka M, Yeh C-H, Tian M, Chen H, Cain DW, et al. Immune checkpoint modulation enhances HIV-1 antibody induction. Nat Commun. 2020 Feb 19;11(1):948.
Bradley, Todd, et al. “Immune checkpoint modulation enhances HIV-1 antibody induction.” Nat Commun, vol. 11, no. 1, Feb. 2020, p. 948. Pubmed, doi:10.1038/s41467-020-14670-w.
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, Bowman CM, Bouton-Verville H, Santra S, Wiehe K, Lewis MG, Ogbe A, Borrow P, Montefiori D, Bonsignori M, Anthony Moody M, Verkoczy L, Saunders KO, Ahmed R, Mascola JR, Kelsoe G, Alt FW, Haynes BF. Immune checkpoint modulation enhances HIV-1 antibody induction. Nat Commun. 2020 Feb 19;11(1):948.

Published In

Nat Commun

DOI

10.1038/s41467-020-14670-w

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