IgG3 subclass antibodies recognize antigenically drifted influenza viruses and SARS-CoV-2 variants through efficient bivalent binding.

TitleIgG3 subclass antibodies recognize antigenically drifted influenza viruses and SARS-CoV-2 variants through efficient bivalent binding.
Publication TypeJournal Article
Year of Publication2023
AuthorsBolton MJ, Santos JJS, Arevalo CP, Griesman T, Watson M, Li SHang, Bates P, Ramage H, Wilson PC, Hensley SE
JournalProc Natl Acad Sci U S A
Volume120
Issue35
Paginatione2216521120
Date Published2023 Aug 29
ISSN1091-6490
KeywordsAntibodies, Monoclonal, Antibodies, Viral, COVID-19, Humans, Immunoglobulin G, Orthomyxoviridae, SARS-CoV-2
Abstract

The constant domains of antibodies are important for effector functions, but less is known about how they can affect binding and neutralization of viruses. Here, we evaluated a panel of human influenza virus monoclonal antibodies (mAbs) expressed as IgG1, IgG2, or IgG3. We found that many influenza virus-specific mAbs have altered binding and neutralization capacity depending on the IgG subclass encoded and that these differences result from unique bivalency capacities of the subclasses. Importantly, subclass differences in antibody binding and neutralization were greatest when the affinity for the target antigen was reduced through antigenic mismatch. We found that antibodies expressed as IgG3 bound and neutralized antigenically drifted influenza viruses more effectively. We obtained similar results using a panel of SARS-CoV-2-specific mAbs and the antigenically advanced B.1.351 and BA.1 strains of SARS-CoV-2. We found that a licensed therapeutic mAb retained neutralization breadth against SARS-CoV-2 variants when expressed as IgG3, but not IgG1. These data highlight that IgG subclasses are not only important for fine-tuning effector functionality but also for binding and neutralization of antigenically drifted viruses.

DOI10.1073/pnas.2216521120
Custom 1

https://www.ncbi.nlm.nih.gov/pubmed/37603748?dopt=Abstract

Alternate JournalProc Natl Acad Sci U S A
PubMed ID37603748
PubMed Central IDPMC10469028
Grant List75N93021C00015 / AI / NIAID NIH HHS / United States
R01 AI108686 / AI / NIAID NIH HHS / United States

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