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

Published on Sep 8, 2016in Cell36.216
· DOI :10.1016/J.CELL.2016.07.029
Ming Tian17
Estimated H-index: 17
(Harvard University),
Cheng Cheng23
Estimated H-index: 23
(Vaccine Research Center)
+ 37 AuthorsFrederick W. Alt156
Estimated H-index: 156
(Harvard University)
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.
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