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Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody.

Publication ,  Journal Article
Bonsignori, M; Zhou, T; Sheng, Z; Chen, L; Gao, F; Joyce, MG; Ozorowski, G; Chuang, G-Y; Schramm, CA; Wiehe, K; Alam, SM; Bradley, T; Lu, X ...
Published in: Cell
April 7, 2016

Antibodies with ontogenies from VH1-2 or VH1-46-germline genes dominate the broadly neutralizing response against the CD4-binding site (CD4bs) on HIV-1. Here, we define with longitudinal sampling from time-of-infection the development of a VH1-46-derived antibody lineage that matured to neutralize 90% of HIV-1 isolates. Structures of lineage antibodies CH235 (week 41 from time-of-infection, 18% breadth), CH235.9 (week 152, 77%), and CH235.12 (week 323, 90%) demonstrated the maturing epitope to focus on the conformationally invariant portion of the CD4bs. Similarities between CH235 lineage and five unrelated CD4bs lineages in epitope focusing, length-of-time to develop breadth, and extraordinary level of somatic hypermutation suggested commonalities in maturation among all CD4bs antibodies. Fortunately, the required CH235-lineage hypermutation appeared substantially guided by the intrinsic mutability of the VH1-46 gene, which closely resembled VH1-2. We integrated our CH235-lineage findings with a second broadly neutralizing lineage and HIV-1 co-evolution to suggest a vaccination strategy for inducing both lineages.

Duke Scholars

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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

April 7, 2016

Volume

165

Issue

2

Start / End Page

449 / 463

Location

United States

Related Subject Headings

  • Sequence Alignment
  • Molecular Sequence Data
  • Models, Molecular
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • Developmental Biology
  • B-Lymphocytes
 

Citation

APA
Chicago
ICMJE
MLA
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Bonsignori, M., Zhou, T., Sheng, Z., Chen, L., Gao, F., Joyce, M. G., … Haynes, B. F. (2016). Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody. Cell, 165(2), 449–463. https://doi.org/10.1016/j.cell.2016.02.022
Bonsignori, Mattia, Tongqing Zhou, Zizhang Sheng, Lei Chen, Feng Gao, M Gordon Joyce, Gabriel Ozorowski, et al. “Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody.Cell 165, no. 2 (April 7, 2016): 449–63. https://doi.org/10.1016/j.cell.2016.02.022.
Bonsignori M, Zhou T, Sheng Z, Chen L, Gao F, Joyce MG, et al. Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody. Cell. 2016 Apr 7;165(2):449–63.
Bonsignori, Mattia, et al. “Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody.Cell, vol. 165, no. 2, Apr. 2016, pp. 449–63. Pubmed, doi:10.1016/j.cell.2016.02.022.
Bonsignori M, Zhou T, Sheng Z, Chen L, Gao F, Joyce MG, Ozorowski G, Chuang G-Y, Schramm CA, Wiehe K, Alam SM, Bradley T, Gladden MA, Hwang K-K, Iyengar S, Kumar A, Lu X, Luo K, Mangiapani MC, Parks RJ, Song H, Acharya P, Bailer RT, Cao A, Druz A, Georgiev IS, Kwon YD, Louder MK, Zhang B, Zheng A, Hill BJ, Kong R, Soto C, NISC Comparative Sequencing Program, Mullikin JC, Douek DC, Montefiori DC, Moody MA, Shaw GM, Hahn BH, Kelsoe G, Hraber PT, Korber BT, Boyd SD, Fire AZ, Kepler TB, Shapiro L, Ward AB, Mascola JR, Liao H-X, Kwong PD, Haynes BF. Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody. Cell. 2016 Apr 7;165(2):449–463.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

April 7, 2016

Volume

165

Issue

2

Start / End Page

449 / 463

Location

United States

Related Subject Headings

  • Sequence Alignment
  • Molecular Sequence Data
  • Models, Molecular
  • Humans
  • HIV-1
  • HIV Infections
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • Developmental Biology
  • B-Lymphocytes