Multiscale affinity maturation simulations to elicit broadly neutralizing antibodies against HIV
Name
journal.pcbi.1009391.pdf
Description
Published version
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2.08 MB
Format
Adobe PDF
Checksum (MD5)
73aafcb79a2cd1152374722c23a69943
Author(s)
Conti, Simone
Ovchinnikov, Victor
Faris, Jonathan G
Chakraborty, Arup K
Karplus, Martin
Sprenger, Kayla G
Date Issued
April 22, 2022
Journal
PLOS Computational Biology
Publisher
Public Library of Science
Citation
Conti S, Ovchinnikov V, Faris JG, Chakraborty AK, Karplus M, Sprenger KG (2022). Multiscale affinity maturation simulations to elicit broadly neutralizing antibodies against HIV. PLoS Comput Biol 18(4): e1009391.
Version
Final published version
Abstract
The design of vaccines against highly mutable pathogens, such as HIV and influenza, requires a detailed understanding of how the adaptive immune system responds to encountering multiple variant antigens (Ags). Here, we describe a multiscale model of B cell receptor (BCR) affinity maturation that employs actual BCR nucleotide sequences and treats BCR/Ag interactions in atomistic detail. We apply the model to simulate the maturation of a broadly neutralizing Ab (bnAb) against HIV. Starting from a germline precursor sequence of the VRC01 anti-HIV Ab, we simulate BCR evolution in response to different vaccination protocols and different Ags, which were previously designed by us. The simulation results provide qualitative guidelines for future vaccine design and reveal unique insights into bnAb evolution against the CD4 binding site of HIV. Our model makes possible direct comparisons of simulated BCR populations with results of deep sequencing data, which will be explored in future applications.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Institute for Medical Engineering and Science
Massachusetts Institute of Technology. Department of Physics
Ragon Institute of MGH, MIT and Harvard
Massachusetts Institute of Technology. Department of Chemistry
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Creative Commons Attribution
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DOI of Published Version
10.1371/journal.pcbi.1009391
