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

TitleInduction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires.
Publication TypeJournal Article
Year of Publication2016
AuthorsTian M, Cheng C, Chen X, Duan H, Cheng H-L, Dao M, Sheng Z, Kimble M, Wang L, Lin S, Schmidt SD, Du Z, M Joyce G, Chen Y, Dekosky BJ, Chen Y, 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
JournalCell
Volume166
Issue6
Pagination1471-1484.e18
Date Published09/08/2016
ISSN0092-8674
Abstract

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.

DOI10.1016/j.cell.2016.07.029
Alternate JournalCell
PubMed ID27610571
Grant ListR01 AI020047 / AI / NIAID NIH HHS / United States
U19 AI109632 / AI / NIAID NIH HHS / United States
P01 AI094419 / AI / NIAID NIH HHS / United States
UM1 AI100645 / AI / NIAID NIH HHS / United States
R01 AI077595 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
/ HHMI / HHMI / United States
P01 AI104722 / AI / NIAID NIH HHS / United States
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