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

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

David Charles Montefiori
Author David Charles Montefiori Surgery, Surgical Sciences
Michael Anthony Moody
Author Michael Anthony Moody Pediatrics, Infectious Diseases
Wilton Bryan Williams
Author Wilton Bryan Williams Surgery, Surgical Sciences
S. Munir Alam
Author S. Munir Alam Medicine, Duke Human Vaccine Institute
Kevin J Wiehe
Author Kevin J Wiehe Medicine, Duke Human Vaccine Institute
Kevin O'Neil Saunders
Author Kevin O'Neil Saunders Surgery, Surgical Sciences
Feng Gao
Author Feng Gao Medicine, Infectious Diseases
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/s41467-017-01336-3

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

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ICMJE
MLA
NLM
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

10.1038/s41467-017-01336-3

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