ArticlePloS one2014
Modeling neutralization kinetics of HIV by broadly neutralizing monoclonal antibodies in genital secretions coating the cervicovaginal mucosa.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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
21 citing papers in PubMed, 35 citations in OpenAlex.
- Thixo-viscoelastoplastic rheological characterisation of human mucus using a multimode BMP constitutive equation approach.Scientific reports · 2025Article
- Spatial Pharmacokinetic and Pharmacodynamic Modeling in Airway Mucus.Clinical pharmacokinetics · 2025Article
- The power of weak, transient interactions across biology: A paradigm of emergent behavior.Physica D. Nonlinear phenomena · 2023Article
- Antiviral neutralizing antibodies: from in vitro to in vivo activity.Nature reviews. Immunology · 2023Review
- Tissue-resident memory T cells trigger rapid exudation and local antibody accumulation.Mucosal immunology · 2023Article
- Antibody protection from SARS-CoV-2 respiratory tract exposure and infection.Journal of theoretical biology · 2023Article
- 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
- Modeling HIV-1 Within-Host Dynamics After Passive Infusion of the Broadly Neutralizing Antibody VRC01.Frontiers in immunology · 2021Article
- Antibody-mediated trapping in biological hydrogels is governed by sugar-sugar hydrogen bonds.Acta biomaterialia · 2020Article
- The cervicovaginal mucus barrier to HIV-1 is diminished in bacterial vaginosis.PLoS pathogens · 2020Article
- Robust antigen-specific tuning of the nanoscale barrier properties of biogels using matrix-associating IgG and IgM antibodies.Acta biomaterialia · 2019Article
- Technological strategies to estimate and control diffusive passage times through the mucus barrier in mucosal drug delivery.Advanced drug delivery reviews · 2018Review
- Physicochemical properties of mucus and their impact on transmucosal drug delivery.International journal of pharmaceutics · 2017Review
- Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters.PLoS pathogens · 2017Article
- Fusion of the mouse IgG1 Fc domain to the VHH fragment (ARP1) enhances protection in a mouse model of rotavirus.Scientific reports · 2016Article
- Broadly neutralizing antibody specificities detected in the genital tract of HIV-1 infected women.AIDS (London, England) · 2016Article
- Using Computational Modeling To Optimize the Design of Antibodies That Trap Viruses in Mucus.ACS infectious diseases · 2016Article
- Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection.PLoS pathogens · 2015Article
- Predicting first traversal times for virions and nanoparticles in mucus with slowed diffusion.Biophysical journal · 2015Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Eliciting broadly neutralizing antibodies (bnAb) in cervicovaginal mucus (CVM) represents a promising "first line of defense" strategy to reduce vaginal HIV transmission. However, it remains unclear what levels of bnAb must be present in CVM to effectively reduce infection. We approached this complex question by modeling the dynamic tally of bnAb coverage on HIV. This analysis introduces a critical, timescale-dependent competition: to protect, bnAb must accumulate at sufficient stoichiometry to neutralize HIV faster than virions penetrate CVM and reach target cells. We developed a model that incorporates concentrations and diffusivities of HIV and bnAb in semen and CVM, kinetic rates for binding (kon) and unbinding (koff) of select bnAb, and physiologically relevant thicknesses of CVM and semen layers. Comprehensive model simulations lead to robust conclusions about neutralization kinetics in CVM. First, due to the limited time virions in semen need to penetrate CVM, substantially greater bnAb concentrations than in vitro estimates must be present in CVM to neutralize HIV. Second, the model predicts that bnAb with more rapid kon, almost independent of koff, should offer greater neutralization potency in vivo. These findings suggest the fastest arriving virions at target cells present the greatest likelihood of infection. It also implies the marked improvements in in vitro neutralization potency of many recently discovered bnAb may not translate to comparable reduction in the bnAb dose needed to confer protection against initial vaginal infections. Our modeling framework offers a valuable tool to gaining quantitative insights into the dynamics of mucosal immunity against HIV and other infectious diseases.
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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.