ArticleJournal of virology2014
Mechanism and significance of cell type-dependent neutralization of flaviviruses.
Article in Journal of virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 74 citations in OpenAlex.
- Dengue viruses cluster antigenically but not as discrete serotypes.Science (New York, N.Y.) · 2015Trial
- Conformational dynamics of the HIV-1 envelope glycoprotein from CRF01_AE is associated with susceptibility to antibody-dependent cellular cytotoxicity.Journal of virology · 2026Article
- The asymmetric opening of HIV-1 Env by a potent CD4 mimetic enables anti-coreceptor binding site antibodies to mediate ADCC.Nature communications · 2025Article
- Targeted Lymph Node Immunization with Serotype-Specific Dengue VLP Vaccines Enhances Antibody Avidity and Specificity.Vaccines · 2025Article
- Molecular basis for the increased fusion activity of the Ebola virus glycoprotein epidemic variant A82V: Insights from simulations and experiments.Cell reports · 2025Article
- Complement-mediated enhancement of SARS-CoV-2 antibody neutralisation potency in vaccinated individuals.Nature communications · 2025Article
- The combination of three CD4-induced antibodies targeting highly conserved Env regions with a small CD4-mimetic achieves potent ADCC activity.Journal of virology · 2024Article
- Simultaneous quantitation of neutralizing antibodies against all four dengue virus serotypes using optimized reporter virus particles.Journal of virology · 2024Article
- Seasonal human coronaviruses OC43, 229E, and NL63 induce cell surface modulation of entry receptors and display host cell-specific viral replication kinetics.Microbiology spectrum · 2024Article
- The combination of three CD4-induced antibodies targeting highly conserved Env regions with a small CD4-mimetic achieves potent ADCC activity.bioRxiv : the preprint server for biology · 2024Article
- Review
- Protection against symptomatic dengue infection by neutralizing antibodies varies by infection history and infecting serotype.Nature communications · 2024Article
- Regulation of Ebola GP conformation and membrane binding by the chemical environment of the late endosome.PLoS pathogens · 2023Article
- Research progress in methods for detecting neutralizing antibodies against SARS-CoV-2.Analytical biochemistry · 2023Review
- prM-reactive antibodies reveal a role for partially mature virions in dengue virus pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Neutralizing antibodies protect mice against Venezuelan equine encephalitis virus aerosol challenge.The Journal of experimental medicine · 2022Article
- Longitudinal waning of mRNA vaccine-induced neutralizing antibodies against SARS-CoV-2 detected by an LFIA rapid test.Antibody therapeutics · 2022Article
- Recent Developments in SARS-CoV-2 Neutralizing Antibody Detection Methods.Current medical science · 2021Review
- Dengue Virus Serotype 1 Conformational Dynamics Confers Virus Strain-Dependent Patterns of Neutralization by Polyclonal Sera.Journal of virology · 2021Article
- Broadly neutralizing monoclonal antibodies protect against multiple tick-borne flaviviruses.The Journal of experimental medicine · 2021Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledThe production of neutralizing antibodies (NAbs) is a correlate of protection for many human vaccines, including currently licensed vaccines against flaviviruses. NAbs are typically measured using a plaque reduction neutralization test (PRNT). Despite its extensive use, parameters that impact the performance of the PRNT have not been investigated from a mechanistic perspective. The results of a recent phase IIb clinical trial of a tetravalent dengue virus (DENV) vaccine suggest that NAbs, as measured using a PRNT performed with Vero cells, do not correlate with protection. This surprising finding highlights the importance of understanding how well the PRNT captures the complexity of the NAb response to DENV. In this study, we demonstrated that the structural heterogeneity of flaviviruses arising from inefficient virion maturation impacts the results of neutralization assays in a cell type-dependent manner. Neutralization titers of several monoclonal antibodies were significantly reduced when assayed on Vero cells compared to Raji cells expressing DC-SIGNR. This pattern can be explained by differences in the efficiency with which partially mature flaviviruses attach to each cell type, rather than a differential capacity of antibody to block infection. Vero cells are poorly permissive to the fraction of virions that are most sensitive to neutralization. Analysis of sera from recipients of live-attenuated monovalent DENV vaccine candidates revealed a strong correlation between the sensitivity of serum antibodies to the maturation state of DENV and cell type-dependent patterns of neutralization. Cross-reactive patterns of neutralization may be underrepresented by the "gold-standard" PRNT that employs Vero cells. IMPORTANCE: Cell type-dependent patterns of neutralization describe a differential capacity of antibodies to inhibit virus infection when assayed on multiple cellular substrates. In this study, we established a link between antibodies that neutralize infection in a cell type-dependent fashion and those sensitive to the maturation state of the flavivirus virion. We demonstrated that cell type-dependent neutralization reflects a differential capacity to measure neutralization of viruses that are incompletely mature. Partially mature virions that most efficiently bind maturation state-sensitive antibodies are poorly represented by assays typically used in support of flavivirus vaccine development. The selection of cellular substrate for neutralization assays may significantly impact evaluation of the neutralization potency of the polyclonal response. These data suggest that current assays do not adequately capture the full complexity of the neutralizing antibody response and may hinder the identification of correlates of protection following flavivirus vaccination.
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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.