| Literature DB >> 27610571 |
Ming Tian1, Cheng Cheng2, Xuejun Chen2, Hongying Duan2, Hwei-Ling Cheng1, Mai Dao1, Zizhang Sheng3, Michael Kimble1, Lingshu Wang2, Sherry Lin1, Stephen D Schmidt2, Zhou Du1, M Gordon Joyce2, Yiwei Chen1, Brandon J DeKosky2, Yimin Chen1, Erica Normandin2, Elizabeth Cantor1, Rita E Chen2, Nicole A Doria-Rose2, Yi Zhang2, Wei Shi2, Wing-Pui Kong2, Misook Choe2, Amy R Henry2, Farida Laboune2, Ivelin S Georgiev4, Pei-Yi Huang1, Suvi Jain1, Andrew T McGuire5, Eric Georgeson6, Sergey Menis6, Daniel C Douek2, William R Schief7, Leonidas Stamatatos5, Peter D Kwong2, Lawrence Shapiro8, Barton F Haynes9, John R Mascola10, Frederick W Alt11.
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.Entities:
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Year: 2016 PMID： 27610571 PMCID： PMC5103708 DOI： 10.1016/j.cell.2016.07.029
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582