Evidence map›Paper›PMID 38933606›Full record

ArticlePathogens & immunity2024

Characteristics and Functions of Infection-enhancing Antibodies to the N-terminal Domain of SARS-CoV-2.

Ruth I Connor, Mrunal Sakharkar, C Garrett Rappazzo, Chengzi I Kaku, Nicholas C Curtis, Seungmin Shin, Wendy F Wieland-Alter, Jordan Wentworth, Daniel W Mielcarz, Joshua A Weiner and 4 more

Abstract read
In one paragraph

Article in Pathogens & immunity, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Ruth I ConnorDepartment of Pediatrics, Geisel School of Medicine, Dartmouth Health, Lebanon, New Hampshire.
Mrunal SakharkarAdimab LLC, Lebanon, New Hampshire.
C Garrett RappazzoAdimab LLC, Lebanon, New Hampshire.
Chengzi I KakuAdimab LLC, Lebanon, New Hampshire.
Nicholas C CurtisThayer School of Engineering, Dartmouth College, Hanover, New Hampshire.
Seungmin ShinThayer School of Engineering, Dartmouth College, Hanover, New Hampshire.
Wendy F Wieland-AlterDepartment of Pediatrics, Geisel School of Medicine, Dartmouth Health, Lebanon, New Hampshire.
Jordan WentworthDartLab, Dartmouth Cancer Center, Geisel School of Medicine, Lebanon, New Hampshire.
Daniel W MielcarzDartLab, Dartmouth Cancer Center, Geisel School of Medicine, Lebanon, New Hampshire.
Joshua A WeinerThayer School of Engineering, Dartmouth College, Hanover, New Hampshire.
Margaret E AckermanDepartment of Microbiology and Immunology, Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire.
Laura M WalkerAdimab LLC, Lebanon, New Hampshire.
Jiwon LeeThayer School of Engineering, Dartmouth College, Hanover, New Hampshire.
Peter F WrightDepartment of Pediatrics, Geisel School of Medicine, Dartmouth Health, Lebanon, New Hampshire.

Funding

Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Fred W Kolling IV · 1985 to 2026
$91.3M
Understanding the role of RNA-binding protein mutations in cancerP20GM113132 · NIGMS · DARTMOUTH COLLEGE · PI MADDEN, DEAN R · 2016 to 2025
$25.9M
NCI NIH HHS P30 CA023108NIGMS NIH HHS P20 GM113132
6 · The paper itself

Abstract

Background: Fcγ-receptor (FcγR)-independent enhancement of SARS-CoV-2 infection mediated by N-terminal domain (NTD)-binding monoclonal antibodies (mAbs) has been observed Methods: We characterized 1,213 SARS-CoV-2 spike (S)-binding mAbs derived from COVID-19 convalescent patients for binding specificity to the SARS-CoV-2 S protein, VH germ-line usage, and affinity maturation. Infection enhancement in a vesicular stomatitis virus (VSV)-SARS-CoV-2 S pseudovirus (PV) assay was characterized in respiratory and intestinal epithelial cell lines, and against SARS-CoV-2 variants of concern (VOC). Proteomic deconvolution of the serum antibody repertoire was used to determine functional attributes of secreted NTD-binding mAbs. Results: We identified 72/1213 (5.9%) mAbs that enhanced SARS-CoV-2 infection in a PV assay. The majority (68%) of these mAbs recognized the NTD, were identified in patients with mild and severe disease, and persisted for at least 5 months post-infection. Infection enhancement by NTD-binding mAbs was not observed in intestinal and respiratory epithelial cell lines and was diminished or lost against SARS-CoV-2 VOC. Proteomic deconvolution of the serum antibody repertoire from 2 of the convalescent patients identified, for the first time, NTD-binding, infection-enhancing mAbs among the circulating immunoglobulins directly isolated from serum. Functional analysis of these mAbs demonstrated robust activation of FcγRIIIa associated with antibody binding to recombinant S proteins. Conclusions: Functionally active NTD-specific mAbs arise frequently during natural infection and can last as major serum clonotypes during convalescence. These antibodies display functional attributes that include FcγR activation, and may be selected against by mutations in NTD associated with SARS-CoV-2 VOC.

Indexed as

antibodiesCOVID-19FcR activationinfection enhancementSARS-CoV-2serum clonotypesvariants of concern

Identifiers

PMID38933606
PMCPMC11197847

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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.