Journal
IMMUNITY
Volume 53, Issue 4, Pages 840-+Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2020.09.007
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Funding
- NIH/NIAID [R01 AI104384, P01 AI138212]
- Office of Science, Office of Basic Energy Sciences of the United States Department of Energy [DE-AC0205CH11231]
- United States Department of Energy, Office of Science, Office of Advanced Scientific Computing Research, Scientific Discovery through Advanced Computing (SciDAC) program
- Stanford's Bio-X Interdisciplinary Initiatives Seed Grants Program
- James B. Pendleton Charitable Trust of the Formulatrix robotic instrumentation
- National Institute of General Medical Sciences
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Activating precursor B cell receptors of HIV-1 broadly neutralizing antibodies requires specifically designed immunogens. Here, we compared the abilities of three such germline-targeting immunogens against the VRC01-class receptors to activate the targeted B cells in transgenic mice expressing the germline VH of the VRC01 antibody but diverse mouse light chains. lmmunogen-specific VRC01 -like B cells were isolated at different time points after immunization, their VH and VL genes were sequenced, and the corresponding antibodies characterized, VRC01 B cell sub-populations with distinct cross-reactivity properties were activated by each immunogen, and these differences correlated with distinct biophysical and biochemical features of the germline-targeting immunogens. Our study indicates that the design of effective immunogens to activate B cell receptors leading to protective HIV-1 antibodies will require a better understanding of how the biophysical properties of the epitope and its surrounding surface on the germline-targeting immunogen influence its interaction with the available receptor variants in vivo.
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