High-affinity, neutralizing antibodies to SARS-CoV-2 can be made in absence of T follicular helper cells

  

View ORCID ProfileJennifer S. Chen,  View ORCID ProfileRyan D. Chow, Eric Song, Tianyang Mao, Benjamin Israelow, Kathy Kamath, Joel Bozekowski, Winston A. Haynes, Renata B. Filler, Bridget L. Menasche, Jin Wei, Mia Madel Alfajaro, Wenzhi Song, Lei Peng, Lauren Carter, Jason S. Weinstein, Uthaman Gowthaman,  View ORCID ProfileSidi Chen, Joe Craft, John C. Shon,  View ORCID ProfileAkiko Iwasaki, Craig B. Wilen, Stephanie C. Eisenbarth

doi: https://doi.org/10.1101/2021.06.10.447982

This article is a preprint and has not been certified by peer review [what does this mean?].

PDF: https://www.biorxiv.org/content/10.1101/2021.06.10.447982v1.full.pdf

Abstract

T follicular helper (Tfh) cells are the conventional drivers of protective, germinal center (GC)-based antiviral antibody responses. However, loss of Tfh cells and GCs has been observed in patients with severe COVID-19. As T cell-B cell interactions and immunoglobulin class switching still occur in these patients, non-canonical pathways of antibody production may be operative during SARS-CoV-2 infection. We found that both Tfh-dependent and -independent antibodies were induced against SARS-CoV-2 as well as influenza A virus. Tfh-independent responses were mediated by a population we call lymph node (LN)-Th1 cells, which remain in the LN and interact with B cells outside of GCs to promote high-affinity but broad-spectrum antibodies. Strikingly, antibodies generated in the presence and absence of Tfh cells displayed similar neutralization potency against homologous SARS-CoV-2 as well as the B.1.351 variant of concern. These data support a new paradigm for the induction of B cell responses during viral infection that enables effective, neutralizing antibody production to complement traditional GCs and even compensate for GCs damaged by viral inflammation.

Competing Interest Statement

KK, JB, WAH, and JCS declare the following competing interests: ownership of stocks or shares at Serimmune, paid employment at Serimmune, and patent applications on behalf of Serimmune. Yale University (CBW) has a patent pending entitled "Compounds and Compositions for Treating, Ameliorating, and/or Preventing SARS-CoV-2 Infection and/or Complications Thereof." Yale University has committed to rapidly executable nonexclusive royalty-free licenses to intellectual property rights for the purpose of making and distributing products to prevent, diagnose, and treat COVID-19 infection during the pandemic and for a short period thereafter.

https://www.biorxiv.org/content/10.1101/2021.06.10.447982v1