Skip to main content
SearchLoginLogin or Signup

Review of "Characteristics and Functions of Infection-Enhancing Antibodies to the N-Terminal Domain of SARS-CoV-2"

Reviewers: D Standley (Osaka University) | 📘📘📘📘📘

Published onJun 30, 2024
Review of "Characteristics and Functions of Infection-Enhancing Antibodies to the N-Terminal Domain of SARS-CoV-2"
key-enterThis Pub is a Review of
Characteristics and functions of infection-enhancing antibodies to the N-terminal domain of SARS-CoV-2
Characteristics and functions of infection-enhancing antibodies to the N-terminal domain of SARS-CoV-2
Description

ABSTRACT Characterization of functional antibody responses to the N-terminal domain (NTD) of the SARS-CoV-2 spike (S) protein has included identification of both potent neutralizing activity and putative enhancement of infection. Fcγ-receptor (FcγR)-independent enhancement of SARS-CoV-2 infection mediated by NTD-binding monoclonal antibodies (mAbs) has been observed in vitro, but the functional significance of these antibodies in vivo is not clear. Here we studied 1,213 S-binding mAbs derived from longitudinal sampling of B-cells collected from eight COVID-19 convalescent patients and identified 72 (5.9%) mAbs that enhanced infection in a VSV-SARS-CoV-2-S-Wuhan pseudovirus (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 five months post-infection. Enhancement of PV infection by NTD-binding mAbs was not observed using intestinal (Caco-2) and respiratory (Calu-3) epithelial cells as infection targets and was diminished or lost against SARS-CoV-2 variants of concern (VOC). Proteomic deconvolution of the serum antibody repertoire from two of the convalescent subjects identified, for the first time, NTD-binding, infection-enhancing mAbs among the circulating immunoglobulins directly isolated from serum (i.e., functionally secreted antibody). Functional analysis of these mAbs demonstrated robust activation of FcγRIIIa associated with antibody binding to recombinant S proteins. Taken together, these findings suggest functionally active NTD-specific mAbs arise frequently during natural infection and can last as major serum clonotypes during convalescence. These antibodies display diverse attributes that include FcγR activation, and may be selected against by mutations in NTD associated with SARS-CoV-2 VOC.

To read the original manuscript, click the link above.

Summary of Reviews: This study analyzed antibodies from COVID-19 convalescent patients and found that some enhanced infection in a specific pseudovirus assay, with most targeting the NTD of the spike protein. These antibodies were present in both mild and severe cases and persisted for at least 5 months. However, this enhancement was not observed in all cell types. The reviewer suggests further analysis of the diversity of these antibodies and validate the sequencing methods used in the study.

Reviewer 1 (Daron S…) | 📘📘📘📘📘

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

To read the reviews, click the links below. 

Comments
0
comment
No comments here
Why not start the discussion?