ArticleBiophysical journal2014
Transient antibody-mucin interactions produce a dynamic molecular shield against viral invasion.
Article in Biophysical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
36 citing papers in PubMed, 53 citations in OpenAlex.
- Engineering a "muco-trapping" ACE2-immunoglobulin hybrid with picomolar affinity as an inhaled, pan-variant immunotherapy for COVID-19.Bioengineering & translational medicine · 2024Article
- The interrelation between microbial immunoglobulin coating, vaginal microbiota, ethnicity, and preterm birth.Microbiome · 2024Article
- Inferring Stochastic Rates from Heterogeneous Snapshots of Particle Positions.Bulletin of mathematical biology · 2024Article
- Tethering of soluble immune effectors to mucin and chitin reflects a convergent and dynamic role in gut immunity.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- The power of weak, transient interactions across biology: A paradigm of emergent behavior.Physica D. Nonlinear phenomena · 2023Article
- Article
- Antibody protection from SARS-CoV-2 respiratory tract exposure and infection.Journal of theoretical biology · 2023Article
- Physiology and pathophysiology of human airway mucus.Physiological reviews · 2022Review
- Modeling insights into SARS-CoV-2 respiratory tract infections prior to immune protection.Biophysical journal · 2022Article
- The biophysical principles underpinning muco-trapping functions of antibodies.Human vaccines & immunotherapeutics · 2022Review
- Evaluation of strategies to modify Anti-SARS-CoV-2 monoclonal antibodies for optimal functionality as therapeutics.PloS one · 2022Article
- The Cervicovaginal Mucus Barrier.International journal of molecular sciences · 2020Review
- Development of human ectocervical tissue models with physiologic endocrine and paracrine signaling†.Biology of reproduction · 2020Article
- Antibody-mediated trapping in biological hydrogels is governed by sugar-sugar hydrogen bonds.Acta biomaterialia · 2020Article
- Mucin CYS domain stiffens the mucus gel hindering bacteria and spermatozoa.Scientific reports · 2019Article
- Design principles of selective transport through biopolymer barriers.Physical review. E · 2019Article
- Robust antigen-specific tuning of the nanoscale barrier properties of biogels using matrix-associating IgG and IgM antibodies.Acta biomaterialia · 2019Article
- Interplay among Vaginal Microbiome, Immune Response and Sexually Transmitted Viral Infections.International journal of molecular sciences · 2019Review
- Herpes simplex virus-binding IgG traps HSV in human cervicovaginal mucus across the menstrual cycle and diverse vaginal microbial composition.Mucosal immunology · 2018Article
- Assessing the Impact of Electrostatic Drag on Processive Molecular Motor Transport.Bulletin of mathematical biology · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Given the difficulty in finding a cure for HIV/AIDS, a promising prevention strategy to reduce HIV transmission is to directly block infection at the portal of entry. The recent Thai RV144 trial offered the first evidence that an antibody-based vaccine may block heterosexual HIV transmission. Unfortunately, the underlying mechanism(s) for protection remain unclear. Here we theoretically examine a hypothesis that builds on our recent laboratory observation: virus-specific antibodies (Ab) can trap individual virions in cervicovaginal mucus (CVM), thereby reducing infection in vivo. Ab are known to have a weak-previously considered inconsequential-binding affinity with the mucin fibers that constitute CVM. However, multiple Ab can bind to the same virion at the same time, which markedly increases the overall Ab-mucin binding avidity, and creates an inheritable virion-mucin affinity. Our model takes into account biologically relevant length and timescales, while incorporating known HIV-Ab affinity and the respective diffusivities of viruses and Ab in semen and CVM. The model predicts that HIV-specific Ab in CVM leads to rapid formation and persistence of an HIV concentration front near the semen/CVM interface, far from the vaginal epithelium. Such an HIV concentration front minimizes the flux of HIV virions reaching target cells, and maximizes their elimination upon drainage of genital secretions. The robustness of the result implies that even exceedingly weak Ab-mucin affinity can markedly reduce the flux of virions reaching target cells. Beyond this specific application, the model developed here is adaptable to other pathogens, mucosal barriers, and geometries, as well as kinetic and diffusional effects, providing a tool for hypothesis testing and producing quantitative insights into the dynamics of immune-mediated protection.
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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.