ArticlePLoS pathogens2023
A single, improbable B cell receptor mutation confers potent neutralization against cytomegalovirus.
Article in PLoS pathogens, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 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.
The trial behind it
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
7 citing papers in PubMed, 9 citations in OpenAlex.
- Computing the inducibility of broadly neutralizing antibodies under a context-dependent model of affinity maturation: applications to sequential vaccine design.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Specificity and functional humoral immune responses induced by the VBI-1501A eVLP HCMV gB vaccine compared to the gB/MF59 vaccine.Human vaccines & immunotherapeutics · 2025Article
- A human cytomegalovirus prefusion-like glycoprotein B subunit vaccine elicits humoral immunity similar to that of postfusion gB in mice.Journal of virology · 2025Article
- Proceedings of the Conference "CMV Vaccine Development-How Close Are We?" (27-28 September 2023).Vaccines · 2024Article
- Computational design of prefusion-stabilized Herpesvirus gB trimers.bioRxiv : the preprint server for biology · 2024Article
- Structure-based design of a soluble human cytomegalovirus glycoprotein B antigen stabilized in a prefusion-like conformation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A broadly neutralizing human monoclonal antibody generated from transgenic mice immunized with HCMV particles limits virus infection and proliferation.Journal of virology · 2024Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Cytomegalovirus (CMV) is a leading cause of infant hearing loss and neurodevelopmental delay, but there are no clinically licensed vaccines to prevent infection, in part due to challenges eliciting neutralizing antibodies. One of the most well-studied targets for CMV vaccines is the viral fusogen glycoprotein B (gB), which is required for viral entry into host cells. Within gB, antigenic domain 2 site 1 (AD-2S1) is a target of potently neutralizing antibodies, but gB-based candidate vaccines have yet to elicit robust responses against this region. We mapped the genealogy of B cells encoding potently neutralizing anti-gB AD-2S1 antibodies from their inferred unmutated common ancestor (UCA) and characterized the binding and function of early lineage ancestors. Surprisingly, we found that a single amino acid heavy chain mutation A33N, which was an improbable mutation rarely generated by somatic hypermutation machinery, conferred broad CMV neutralization to the non-neutralizing UCA antibody. Structural studies revealed that this mutation mediated key contacts with the gB AD-2S1 epitope. Collectively, these results provide insight into potently neutralizing gB-directed antibody evolution in a single donor and lay a foundation for using this B cell-lineage directed approach for the design of next-generation CMV vaccines.
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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 Socratic graph.