ArticleJournal of the Royal Society, Interface2015
A simple mechanistic explanation for original antigenic sin and its alleviation by adjuvants.
Article in Journal of the Royal Society, Interface, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Comparative Immunogenicity of Enhanced Seasonal Influenza Vaccines in Older Adults: A Systematic Review and Meta-analysis.The Journal of infectious diseases · 2019Pooled it
- Long-Term Persistence of Cell-Mediated and Humoral Responses to A(H1N1)pdm09 Influenza Virus Vaccines and the Role of the AS03 Adjuvant System in Adults during Two Randomized Controlled Trials.Clinical and vaccine immunology : CVI · 2017Trial
- Immune imprinting: The persisting influence of the first antigenic encounter with rapidly evolving viruses.Human vaccines & immunotherapeutics · 2024Review
- Review
- Immune Imprinting and Implications for COVID-19.Vaccines · 2023Review
- Effect of seasonal coronavirus immune imprinting on the immunogenicity of inactivated COVID-19 vaccination.Frontiers in immunology · 2023Article
- TLR agonists induce sustained IgG to hemagglutinin stem and modulate T cells following newborn vaccination.NPJ vaccines · 2022Article
- Understanding Antibody Responses in Early Life: Baby Steps towards Developing an Effective Influenza Vaccine.Viruses · 2021Review
- An R848-Conjugated Influenza Virus Vaccine Elicits Robust Immunoglobulin G to Hemagglutinin Stem in a Newborn Nonhuman Primate Model.The Journal of infectious diseases · 2021Article
- Computational investigations of the immune response to repeated influenza infections and vaccinations.Royal Society open science · 2021Article
- Implementing sequence-based antigenic distance calculation into immunological shape space model.BMC bioinformatics · 2020Article
- Protective Antibodies Against Influenza Proteins.Frontiers in immunology · 2019Review
- Recalling the Future: Immunological Memory Toward Unpredictable Influenza Viruses.Frontiers in immunology · 2019Review
- Immune History and Influenza Vaccine Effectiveness.Vaccines · 2018Review
- Serial Vaccination and the Antigenic Distance Hypothesis: Effects on Influenza Vaccine Effectiveness During A(H3N2) Epidemics in Canada, 2010-2011 to 2014-2015.The Journal of infectious diseases · 2017Article
- Immunogenicity of trivalent influenza vaccine in patients with lung cancer undergoing anticancer chemotherapy.Human vaccines & immunotherapeutics · 2017Article
- Immune history and influenza virus susceptibility.Current opinion in virology · 2017Review
- Thyroid Autoantibodies Display both "Original Antigenic Sin" and Epitope Spreading.Frontiers in immunology · 2017Review
Corrections and comments
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Authors and funding
1 author at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A large number of published studies have shown that adaptive immunity to a particular antigen, including pathogen-derived, can be boosted by another, cross-reacting antigen while inducing suboptimal immunity to the latter. Although this phenomenon, called original antigenic sin (OAS), was first reported approximately 70 years ago (Francis et al. 1947 Am. J. Public Health 37, 1013-1016 (doi:10.2105/AJPH.37.8.1013)), its underlying biological mechanisms are still inadequately understood (Kim et al. Proc. Natl Acad. Sci. USA 109, 13 751-13 756 (doi:10.1073/pnas.0912458109)). Here, focusing on the humoral aspects of adaptive immunity, I propose a simple and testable mechanism: that OAS occurs when T regulatory cells induced by the first antigen decrease the dose of the second antigen that is loaded by dendritic cells and available to activate naive lymphocytes. I use both a parsimonious mathematical model and experimental data to confirm the deductive validity of this proposal. This model also explains the puzzling experimental observation that administering certain dendritic cell-activating adjuvants during antigen exposure alleviates OAS. Specifically, the model predicts that such adjuvants will attenuate T regulatory suppression of naive lymphocyte activation. Together, these results suggest additional strategies for redeeming adaptive immunity from the destructive consequences of antigenic 'sin'.
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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.