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Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires.

Publication ,  Journal Article
Tian, M; Cheng, C; Chen, X; Duan, H; Cheng, H-L; Dao, M; Sheng, Z; Kimble, M; Wang, L; Lin, S; Schmidt, SD; Du, Z; Joyce, MG; Chen, Y ...
Published in: Cell
September 8, 2016

The design of immunogens that elicit broadly reactive neutralizing antibodies (bnAbs) has been a major obstacle to HIV-1 vaccine development. One approach to assess potential immunogens is to use mice expressing precursors of human bnAbs as vaccination models. The bnAbs of the VRC01-class derive from the IGHV1-2 immunoglobulin heavy chain and neutralize a wide spectrum of HIV-1 strains via targeting the CD4 binding site of the envelope glycoprotein gp120. We now describe a mouse vaccination model that allows a germline human IGHV1-2(∗)02 segment to undergo normal V(D)J recombination and, thereby, leads to the generation of peripheral B cells that express a highly diverse repertoire of VRC01-related receptors. When sequentially immunized with modified gp120 glycoproteins designed to engage VRC01 germline and intermediate antibodies, IGHV1-2(∗)02-rearranging mice, which also express a VRC01-antibody precursor light chain, can support the affinity maturation of VRC01 precursor antibodies into HIV-neutralizing antibody lineages.

Duke Scholars

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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

September 8, 2016

Volume

166

Issue

6

Start / End Page

1471 / 1484.e18

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Sequence Deletion
  • Precursor Cells, B-Lymphoid
  • Mice
  • Inhibitory Concentration 50
  • Immunoglobulin Heavy Chains
  • Immunization
  • HIV-1
  • HIV Antibodies
  • Gene Expression Regulation
 

Citation

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Tian, M., Cheng, C., Chen, X., Duan, H., Cheng, H.-L., Dao, M., … Alt, F. W. (2016). Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires. Cell, 166(6), 1471-1484.e18. https://doi.org/10.1016/j.cell.2016.07.029
Tian, Ming, Cheng Cheng, Xuejun Chen, Hongying Duan, Hwei-Ling Cheng, Mai Dao, Zizhang Sheng, et al. “Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires.Cell 166, no. 6 (September 8, 2016): 1471-1484.e18. https://doi.org/10.1016/j.cell.2016.07.029.
Tian M, Cheng C, Chen X, Duan H, Cheng H-L, Dao M, et al. Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires. Cell. 2016 Sep 8;166(6):1471-1484.e18.
Tian, Ming, et al. “Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires.Cell, vol. 166, no. 6, Sept. 2016, pp. 1471-1484.e18. Pubmed, doi:10.1016/j.cell.2016.07.029.
Tian M, Cheng C, Chen X, Duan H, Cheng H-L, Dao M, Sheng Z, Kimble M, Wang L, Lin S, Schmidt SD, Du Z, Joyce MG, Chen Y, DeKosky BJ, Normandin E, Cantor E, Chen RE, Doria-Rose NA, Zhang Y, Shi W, Kong W-P, Choe M, Henry AR, Laboune F, Georgiev IS, Huang P-Y, Jain S, McGuire AT, Georgeson E, Menis S, Douek DC, Schief WR, Stamatatos L, Kwong PD, Shapiro L, Haynes BF, Mascola JR, Alt FW. Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires. Cell. 2016 Sep 8;166(6):1471-1484.e18.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

September 8, 2016

Volume

166

Issue

6

Start / End Page

1471 / 1484.e18

Location

United States

Related Subject Headings

  • T-Lymphocytes
  • Sequence Deletion
  • Precursor Cells, B-Lymphoid
  • Mice
  • Inhibitory Concentration 50
  • Immunoglobulin Heavy Chains
  • Immunization
  • HIV-1
  • HIV Antibodies
  • Gene Expression Regulation