期刊
CELL
卷 166, 期 6, 页码 1471-+出版社
CELL PRESS
DOI: 10.1016/j.cell.2016.07.029
关键词
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资金
- NIH [R01AI077595, AI020047, P01 AI094419, U19AI109632, P01-AI104722]
- NIAID, Division of AIDS, Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery (CHAVI-ID) [5UM1 AI100645]
- NIH Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) [1UM1 AI100663]
- intramural research program of the Vaccine Research Center, NIAID, NIH
- International AIDS Vaccine Initiative Neutralizing Antibody Consortium
- International AIDS Vaccine Initiative Neutralizing Antibody Center
- CAVD funding for the IAVI NAC Center
- Ragon Institute of MGH, MIT and Harvard
- HHMI Medical Student Fellowship
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. Wenow 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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