Understanding the role of memory re-activation and cross-reactivity in the defence against SARS-CoV-2

Published on July 23rd, 2021

Authors: Viola Denninger, Catherine Xu, Georg Meisl, Alexey S. Morgunov, Sebastian Fiedler, Alison Ilsley, Marc Emmenegger, Anisa Y. Malik, Monika A. Piziorska, Matthias M. Schneider, Sean R. A. Devenish, Vasilis Kosmoliaptsis, Adriano Aguzzi, Heike Fiegler, Tuomas P. J. Knowles

bioRxiv 2021.07.23.453352 DOI: 10.1101/2021.07.23.453352v1



Recent efforts in understanding the course and severity of SARS‑CoV‑2 infections have highlighted both potential beneficial as well as detrimental effects of cross-reactive antibodies derived from memory immunity. Specifically, due to a significant degree of sequence similarity between SARS‑CoV‑2 and other members of the coronavirus family, memory B‑cells that emerged from previous infections with endemic human coronaviruses (HCoVs) could be re‑activated upon encountering the newly emerged SARS‑CoV‑2, thus prompting the production of cross-reactive antibodies.

Understanding the affinity and concentration of these potentially cross-reactive antibodies to the new SARS‑CoV‑2 antigens is therefore particularly important when assessing both existing immunity against common HCoVs and adverse effects like antibody-dependent enhancement (ADE) in COVID‑19. However, these two fundamental parameters cannot easily be deconvoluted by surface-based assays like enzyme-linked immunosorbent assays (ELISAs) which are routinely used to assess cross-reactivity.

Here, Denninger et al., have used microfluidic antibody-affinity profiling (MAAP) to quantitatively evaluate the humoral immune response in COVID‑19 convalescent patients by determining both antibody affinity and concentration against spike antigens of SARS‑CoV‑2 directly in nine convalescent COVID‑19 patient and three pre-pandemic sera that were seropositive for common HCoVs. All 12 sera contained low concentrations of high affinity antibodies against spike antigens of HCoV‑NL63 and HCoV‑HKU1, indicative of past exposure to these pathogens, while the affinity against the SARS‑CoV‑2 spike protein was lower. These results suggest that cross-reactivity as a consequence of memory re‑activation upon an acute SARS‑CoV‑2 infection may not be a significant factor in generating immunity against SARS‑CoV‑2.

InstrumentFluidity One-W Serum
Therapeutic area: cross-reactivity, SARS-CoV-2, antibody affinity, antibody profiling, COVID

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