ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Simulation of B cell affinity maturation explains enhanced antibody cross-reactivity induced by the polyvalent malaria vaccine AMA1.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 60 citations in OpenAlex.
- A paradigm shift in simulating affinity maturation to elicit broadly neutralizing antibodies.Frontiers in immunology · 2025Review
- Applying valency-based immuno-selection to generate broadly cross-reactive antibodies against influenza hemagglutinins.Nature communications · 2024Article
- A stochastic B cell affinity maturation model to characterize mechanisms of protection for tetravalent dengue vaccine constructs.Frontiers in molecular biosciences · 2023Article
- Design of immunogens for eliciting antibody responses that may protect against SARS-CoV-2 variants.PLoS computational biology · 2022Article
- Assessment on Different Vaccine Formulation Parameters in the Protection against Heterologous Challenge with FMDV in Cattle.Viruses · 2022Article
- Multiscale affinity maturation simulations to elicit broadly neutralizing antibodies against HIV.PLoS computational biology · 2022Article
- Structure-guided envelope trimer design in HIV-1 vaccine development: a narrative review.Journal of the International AIDS Society · 2021Review
- Coevolutionary transitions emerging from flexible molecular recognition and eco-evolutionary feedback.iScience · 2021Article
- Roadmap on biology in time varying environments.Physical biology · 2021Review
- Mechanisms underlying vaccination protocols that may optimally elicit broadly neutralizing antibodies against highly mutable pathogens.Physical review. E · 2021Article
- Stochastic Model of the Adaptive Immune Response Predicts Disease Severity and Captures Enhanced Cross-Reactivity in Natural Dengue Infections.Frontiers in immunology · 2021Article
- Defining and Manipulating B Cell Immunodominance Hierarchies to Elicit Broadly Neutralizing Antibody Responses against Influenza Virus.Cell systems · 2020Article
- Article
- Implementing sequence-based antigenic distance calculation into immunological shape space model.BMC bioinformatics · 2020Article
- Tuning environmental timescales to evolve and maintain generalists.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Mathematical model of broadly reactive plasma cell production.Scientific reports · 2020Article
- Optimization of aProceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Case for Exploiting Cross-Species Epitopes in Malaria Vaccine Design.Frontiers in immunology · 2020Review
- Antigenic Variability.Frontiers in immunology · 2020Article
- Strategies for inducing effective neutralizing antibody responses against HIV-1.Expert review of vaccines · 2019Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polyvalent vaccines use a mixture of Ags representing distinct pathogen strains to induce an immune response that is cross-reactive and protective. However, such approaches often have mixed results, and it is unclear how polyvalency alters the fine specificity of the Ab response and what those consequences might be for protection. In this article, we present a coarse-grain theoretical model of B cell affinity maturation during monovalent and polyvalent vaccinations that predicts the fine specificity and cross-reactivity of the Ab response. We stochastically simulate affinity maturation using a population dynamics approach in which the host B cell repertoire is represented explicitly, and individual B cell subpopulations undergo rounds of stimulation, mutation, and differentiation. Ags contain multiple epitopes and are present in subpopulations of distinct pathogen strains, each with varying degrees of cross-reactivity at the epitope level. This epitope- and strain-specific model of affinity maturation enables us to study the composition of the polyclonal response in granular detail and identify the mechanisms driving serum specificity and cross-reactivity. We applied this approach to predict the Ab response to a polyvalent vaccine based on the highly polymorphic malaria Ag apical membrane antigen-1. Our simulations show how polyvalent apical membrane Ag-1 vaccination alters the selection pressure during affinity maturation to favor cross-reactive B cells to both conserved and strain-specific epitopes and demonstrate how a polyvalent vaccine with a small number of strains and only moderate allelic coverage may be broadly neutralizing. Our findings suggest that altered fine specificity and enhanced cross-reactivity may be a universal feature of polyvalent vaccines.
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Registered trials
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.