ArticleFrontiers in immunology2021
Increased B Cell Selection Stringency In Germinal Centers Can Explain Improved COVID-19 Vaccine Efficacies With Low Dose Prime or Delayed Boost.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Safety and immunogenicity of an optimized self-replicating RNA platform for low dose or single dose vaccine applications: a randomized, open label Phase I study in healthy volunteers.Nature communications · 2025Trial
- Modeling the kinetics of the neutralizing antibody response against SARS-CoV-2 variants after several administrations of Bnt162b2.PLoS computational biology · 2023Trial
- The immunogenicity of an extended dosing interval of BNT162b2 against SARS-CoV-2 Omicron variant among healthy school-aged children, a randomized controlled trial.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2023Trial
- A semi-replicating VSV (srVSV)-based platform for developing broad-spectrum mucosal vaccines against influenza A viruses.Virologica Sinica · 2026Article
- Simultaneous priming of HIV broadly neutralizing antibody precursors to multiple epitopes by germline-targeting mRNA-LNP immunogens in mouse models.Science immunology · 2025Article
- Trade-off between the antiviral and vaccinal effects of antibody therapy in the humoral response to HIV.Journal of the Royal Society, Interface · 2024Article
- Waning Humoral Immune Response Following the Third and Fourth SARS-COV-2 Vaccine: A Cohort Study in Healthcare Workers.Influenza and other respiratory viruses · 2024Article
- The effect of dose-interval on antibody response to mRNA COVID-19 vaccines: a prospective cohort study.Frontiers in immunology · 2024Article
- A nanoparticle vaccine displaying varicella-zoster virus gE antigen induces a superior cellular immune response than a licensed vaccine in mice and non-human primates.Frontiers in immunology · 2024Article
- The race to understand immunopathology in COVID-19: Perspectives on the impact of quantitative approaches to understand within-host interactions.Immunoinformatics (Amsterdam, Netherlands) · 2023Review
- Trained immunity is induced in humans after immunization with an adenoviral vector COVID-19 vaccine.The Journal of clinical investigation · 2023Article
- Mechanistic model for booster doses effectiveness in healthy, cancer, and immunosuppressed patients infected with SARS-CoV-2.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Age-adjusted impact of prior COVID-19 on SARS-CoV-2 mRNA vaccine response.Frontiers in immunology · 2023Article
- Extending the dosing interval of COVID-19 vaccination leads to higher rates of seroconversion in people living with HIV.Frontiers in immunology · 2023Article
- An Evolutionary Paradigm Favoring Cross Talk between Bacterial Two-Component Signaling Systems.mSystems · 2022Article
- Long-term durability of immune responses to the BNT162b2 and mRNA-1273 vaccines based on dosage, age and sex.Scientific reports · 2022Article
- Mechanistic Models of COVID-19: Insights into Disease Progression, Vaccines, and Therapeutics.International journal of antimicrobial agents · 2022Review
- Article
- Modeling suggests that multiple immunizations or infections will reveal the benefits of updating SARS-CoV-2 vaccines.bioRxiv : the preprint server for biology · 2022Article
- A Coarse-Grained Model of Affinity Maturation Indicates the Importance of B-Cell Receptor Avidity in Epitope Subdominance.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The efficacy of COVID-19 vaccines appears to depend in complex ways on the vaccine dosage and the interval between the prime and boost doses. Unexpectedly, lower dose prime and longer prime-boost intervals have yielded higher efficacies in clinical trials. To elucidate the origins of these effects, we developed a stochastic simulation model of the germinal center (GC) reaction and predicted the antibody responses elicited by different vaccination protocols. The simulations predicted that a lower dose prime could increase the selection stringency in GCs due to reduced antigen availability, resulting in the selection of GC B cells with higher affinities for the target antigen. The boost could relax this selection stringency and allow the expansion of the higher affinity GC B cells selected, improving the overall response. With a longer dosing interval, the decay in the antigen with time following the prime could further increase the selection stringency, amplifying this effect. The effect remained in our simulations even when new GCs following the boost had to be seeded by memory B cells formed following the prime. These predictions offer a plausible explanation of the observed paradoxical effects of dosage and dosing interval on vaccine efficacy. Tuning the selection stringency in the GCs using prime-boost dosages and dosing intervals as handles may help improve vaccine efficacies.
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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.