Multiscale affinity maturation simulations to elicit broadly neutralizing antibodies against HIV

Simone Conti, Victor Ovchinnikov, Jonathan G. Faris, Arup K. Chakraborty, Martin Karplus, Kayla G. Sprenger

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageEnglish
Article numbere1009391
JournalPLoS Computational Biology
Issue number4
StatePublished - Apr 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
Copyright: © 2022 Conti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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