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Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations.

Publication ,  Journal Article
Williams, WB; Zhang, J; Jiang, C; Nicely, NI; Fera, D; Luo, K; Moody, MA; Liao, H-X; Alam, SM; Kepler, TB; Ramesh, A; Wiehe, K; Holland, JA ...
Published in: Nat Commun
November 23, 2017

A strategy for HIV-1 vaccine development is to define envelope (Env) evolution of broadly neutralizing antibodies (bnAbs) in infection and to recreate those events by vaccination. Here, we report host tolerance mechanisms that limit the development of CD4-binding site (CD4bs), HCDR3-binder bnAbs via sequential HIV-1 Env vaccination. Vaccine-induced macaque CD4bs antibodies neutralize 7% of HIV-1 strains, recognize open Env trimers, and accumulate relatively modest somatic mutations. In naive CD4bs, unmutated common ancestor knock-in mice Env+B cell clones develop anergy and partial deletion at the transitional to mature B cell stage, but become Env- upon receptor editing. In comparison with repetitive Env immunizations, sequential Env administration rescue anergic Env+ (non-edited) precursor B cells. Thus, stepwise immunization initiates CD4bs-bnAb responses, but immune tolerance mechanisms restrict their development, suggesting that sequential immunogen-based vaccine regimens will likely need to incorporate strategies to expand bnAb precursor pools.

Duke Scholars

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

November 23, 2017

Volume

8

Issue

1

Start / End Page

1732

Location

England

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Models, Molecular
  • Mice, Transgenic
  • Mice
  • Male
  • Macaca mulatta
  • Immunization
  • Immune Tolerance
  • Humans
  • HIV-1
 

Citation

APA
Chicago
ICMJE
MLA
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Williams, W. B., Zhang, J., Jiang, C., Nicely, N. I., Fera, D., Luo, K., … Verkoczy, L. (2017). Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations. Nat Commun, 8(1), 1732. https://doi.org/10.1038/s41467-017-01336-3
Williams, Wilton B., Jinsong Zhang, Chuancang Jiang, Nathan I. Nicely, Daniela Fera, Kan Luo, M Anthony Moody, et al. “Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations.Nat Commun 8, no. 1 (November 23, 2017): 1732. https://doi.org/10.1038/s41467-017-01336-3.
Williams WB, Zhang J, Jiang C, Nicely NI, Fera D, Luo K, et al. Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations. Nat Commun. 2017 Nov 23;8(1):1732.
Williams, Wilton B., et al. “Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations.Nat Commun, vol. 8, no. 1, Nov. 2017, p. 1732. Pubmed, doi:10.1038/s41467-017-01336-3.
Williams WB, Zhang J, Jiang C, Nicely NI, Fera D, Luo K, Moody MA, Liao H-X, Alam SM, Kepler TB, Ramesh A, Wiehe K, Holland JA, Bradley T, Vandergrift N, Saunders KO, Parks R, Foulger A, Xia S-M, Bonsignori M, Montefiori DC, Louder M, Eaton A, Santra S, Scearce R, Sutherland L, Newman A, Bouton-Verville H, Bowman C, Bomze H, Gao F, Marshall DJ, Whitesides JF, Nie X, Kelsoe G, Reed SG, Fox CB, Clary K, Koutsoukos M, Franco D, Mascola JR, Harrison SC, Haynes BF, Verkoczy L. Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations. Nat Commun. 2017 Nov 23;8(1):1732.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

November 23, 2017

Volume

8

Issue

1

Start / End Page

1732

Location

England

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Models, Molecular
  • Mice, Transgenic
  • Mice
  • Male
  • Macaca mulatta
  • Immunization
  • Immune Tolerance
  • Humans
  • HIV-1