ArticleProceedings of the National Academy of Sciences of the United States of America2016
Optimal immunization cocktails can promote induction of broadly neutralizing Abs against highly mutable pathogens.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 72 citations in OpenAlex.
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- Minimal framework for optimizing vaccination protocols targeting highly mutable pathogens.Physical review. E · 2024Article
- Modelling HIV-1 control and remission.NPJ systems biology and applications · 2024Review
- Applying valency-based immuno-selection to generate broadly cross-reactive antibodies against influenza hemagglutinins.Nature communications · 2024Article
- Steering and controlling evolution - from bioengineering to fighting pathogens.Nature reviews. Genetics · 2023Review
- Engaging an HIV vaccine target through the acquisition of low B cell affinity.Nature communications · 2023Article
- Antigen pressure from two founder viruses induces multiple insertions at a single antibody position to generate broadly neutralizing HIV antibodies.PLoS pathogens · 2023Article
- Mechanisms that promote the evolution of cross-reactive antibodies upon vaccination with designed influenza immunogens.Cell reports · 2023Article
- Two complementary features of humoral immune memory confer protection against the same or variant antigens.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Design of immunogens for eliciting antibody responses that may protect against SARS-CoV-2 variants.PLoS computational biology · 2022Article
- From affinity selection to kinetic selection in Germinal Centre modelling.PLoS computational biology · 2022Article
- Multiscale affinity maturation simulations to elicit broadly neutralizing antibodies against HIV.PLoS computational biology · 2022Article
- Moving the needle: Employing deep reinforcement learning to push the boundaries of coarse-grained vaccine models.Frontiers in immunology · 2022Article
- Protein engineering strategies for rational immunogen design.NPJ vaccines · 2021Review
- 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
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Strategies to elicit Abs that can neutralize diverse strains of a highly mutable pathogen are likely to result in a potent vaccine. Broadly neutralizing Abs (bnAbs) against HIV have been isolated from patients, proving that the human immune system can evolve them. Using computer simulations and theory, we study immunization with diverse mixtures of variant antigens (Ags). Our results show that particular choices for the number of variant Ags and the mutational distances separating them maximize the probability of inducing bnAbs. The variant Ags represent potentially conflicting selection forces that can frustrate the Darwinian evolutionary process of affinity maturation. An intermediate level of frustration maximizes the chance of evolving bnAbs. A simple model makes vivid the origin of this principle of optimal frustration. Our results, combined with past studies, suggest that an appropriately chosen permutation of immunization with an optimally designed mixture (using the principles that we describe) and sequential immunization with variant Ags that are separated by relatively large mutational distances may best promote the evolution of bnAbs.
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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.