Evidence map›Paper›PMID 40971634›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2026

Computing the inducibility of broadly neutralizing antibodies under a context-dependent model of affinity maturation: applications to sequential vaccine design.

Joseph Mathews, Elizabeth Van Itallie, Yongkang Li, Kevin Wiehe, Scott C Schmidler

Abstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors.

Joseph MathewsDepartment of Statistical Science, Duke University, Durham, NC, United States.ORCID 0009-0005-3268-9652
Elizabeth Van ItallieDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United States.
Yongkang LiDepartment of Computer Science, Duke University, Durham, NC, United States.
Kevin WieheDuke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, United States.ORCID 0000-0001-9933-9618
Scott C SchmidlerDepartment of Statistical Science, Duke University, Durham, NC, United States.ORCID 0009-0006-3733-3716

Funding

Nonhuman primate studies for development of a prototype HIV vaccine that induces broadly neutralizing antibodiesUM1AI144371 · NIAID · DUKE UNIVERSITY · PI HAYNES, BARTON F. · 2019 to 2025
$190.4M
Virus and Antibody Gene Sequencing CoreP01AI131251 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI Kevin Wiehe · 2017 to 2026
$40.7M
Duke Consortia for HIV/AIDS Vaccine DevelopmentNational Science Foundation DMS-2347859NIAID NIH HHS P01 AI131251NIAID NIH HHS UM1 AI144371NIH HHS UM1AI144371
6 · The paper itself

Abstract

A key challenge in B-cell lineage-based vaccine design is understanding the "inducibility" of target neutralizing antibodies-the ability of these antibodies to be elicited by presentation of an immunogen. Induction relies on a combination of stochastic diversification and immunogen-based selection, and as a result is heavily dependent on the probabilistic accessibility of induction pathways. We explored inducibility using a detailed stochastic model of the somatic hypermutation process-which captures the critical "context-dependence" of sequence mutation rates-coupled to a stochastic population model for B-cell clonal maturation. The model is used to calculate inducibilities for a set of critical mutations required by the HIV broadly neutralizing antibody (bnAb) CH235.12. The results provide insight into barriers to the elicitation of HIV bnAbs and explain experimental results observed in mouse models. Our models enable detailed analysis of maturation pathway probabilities, allowing us to identify opportunities for the design of boosting immunogens aimed at elicitation of CH235.12 via a sequential vaccination regimen.

Indexed as

AIDS VaccinesAntibodies, NeutralizingB-LymphocytesBroadly Neutralizing AntibodiesHIV-1HIV AntibodiesHIV InfectionsModels, ImmunologicalAnimalsAntibody AffinityHumansMiceAIDS VaccinesAntibodies, NeutralizingBroadly Neutralizing AntibodiesHIV Antibodiesbroadly neutralizing antibodycomputational immunologysomatic hypermutation

Identifiers

PMID40971634
PMCPMC12685565

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.