Discriminating cross-reactivity in polyclonal IgG1 responses against SARS-CoV-2 variants of concern

Danique M. H. van Rijswijck, Albert Bondt, Max Hoek, Karlijn van der Straten, Tom G. Caniels, Meliawati Poniman, Dirk Eggink, Chantal Reusken, Godelieve J. de Bree, Rogier W. Sanders, Marit J. van Gils, Albert J. R. Heck

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)

Abstract

Existing assays to measure antibody cross-reactivity against different SARS-CoV-2 spike (S) protein variants lack the discriminatory power to provide insights at the level of individual clones. Using a mass spectrometry-based approach we are able to monitor individual donors’ IgG1 clonal responses following a SARS-CoV-2 infection. We monitor the plasma clonal IgG1 profiles of 8 donors who had experienced an infection by either the wild type Wuhan Hu-1 virus or one of 3 VOCs (Alpha, Beta and Gamma). In these donors we chart the full plasma IgG1 repertoires as well as the IgG1 repertoires targeting the SARS-CoV-2 spike protein trimer VOC antigens. The plasma of each donor contains numerous anti-spike IgG1 antibodies, accounting for <0.1% up to almost 10% of all IgG1s. Some of these antibodies are VOC-specific whereas others do recognize multiple or even all VOCs. We show that in these polyclonal responses, each clone exhibits a distinct cross-reactivity and also distinct virus neutralization capacity. These observations support the need for a more personalized look at the antibody clonal responses to infectious diseases.

Original languageEnglish
Article number6103
JournalNature communications
Volume13
Issue number1
DOIs
Publication statusPublished - 1 Dec 2022

Cite this