ArticleProceedings of the National Academy of Sciences of the United States of America2020
Optimizing immunization protocols to elicit broadly neutralizing antibodies.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 59 citations in OpenAlex.
- Biophysical trade-offs in antibody evolution are resolved by conformation-mediated epistasis.bioRxiv : the preprint server for biology · 2026Article
- Mechanism for evolution of diverse autologous antibodies upon broadly neutralizing antibody therapy of people with HIV.Cell reports · 2025Article
- Article
- Retrospective SARS-CoV-2 human antibody development trajectories are largely sparse and permissive.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Epistatic hotspots organize antibody fitness landscape and boost evolvability.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- A paradigm shift in simulating affinity maturation to elicit broadly neutralizing antibodies.Frontiers in immunology · 2025Review
- Minimal framework for optimizing vaccination protocols targeting highly mutable pathogens.Physical review. E · 2024Article
- Vaccination against rapidly evolving pathogens and the entanglements of memory.Nature immunology · 2024Review
- Discovery, recognized antigenic structures, and evolution of cross-serotype broadly neutralizing antibodies from porcine B-cell repertoires against foot-and-mouth disease virus.PLoS pathogens · 2024Article
- Recapitulation of HIV-1 Neutralization Breadth in Plasma by the Combination of Two Broadly Neutralizing Antibodies from Different Lineages in the Same SHIV-Infected Rhesus Macaque.International journal of molecular sciences · 2024Article
- Immunization-induced antigen archiving enhances local memory CD8+ T cell responses following an unrelated viral infection.NPJ vaccines · 2024Article
- Bringing immunofocusing into focus.NPJ vaccines · 2024Review
- Antibody and Cell-Based Therapies against Virus-Induced Cancers in the Context of HIV/AIDS.Pathogens (Basel, Switzerland) · 2023Review
- Steering and controlling evolution - from bioengineering to fighting pathogens.Nature reviews. Genetics · 2023Review
- Antigen pressure from two founder viruses induces multiple insertions at a single antibody position to generate broadly neutralizing HIV antibodies.PLoS pathogens · 2023Article
- The changing health impact of vaccines in the COVID-19 pandemic: A modeling study.Cell reports · 2023Article
- Mechanisms that promote the evolution of cross-reactive antibodies upon vaccination with designed influenza immunogens.Cell reports · 2023Article
- Article
- Common framework mutations impact antibody interfacial dynamics and flexibility.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural infections and vaccination with a pathogen typically stimulate the production of potent antibodies specific for the pathogen through a Darwinian evolutionary process known as affinity maturation. Such antibodies provide protection against reinfection by the same strain of a pathogen. A highly mutable virus, like HIV or influenza, evades recognition by these strain-specific antibodies via the emergence of new mutant strains. A vaccine that elicits antibodies that can bind to many diverse strains of the virus-known as broadly neutralizing antibodies (bnAbs)-could protect against highly mutable pathogens. Despite much work, the mechanisms by which bnAbs emerge remain uncertain. Using a computational model of affinity maturation, we studied a wide variety of vaccination strategies. Our results suggest that an effective strategy to maximize bnAb evolution is through a sequential immunization protocol, wherein each new immunization optimally increases the pressure on the immune system to target conserved antigenic sites, thus conferring breadth. We describe the mechanisms underlying why sequentially driving the immune system increasingly further from steady state, in an optimal fashion, is effective. The optimal protocol allows many evolving B cells to become bnAbs via diverse evolutionary paths.
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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.