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Cross-reactive serum and memory B cell responses to spike protein in SARS-CoV-2 and endemic coronavirus infection

By Ge Song, Wan-ting He, Sean Callaghan, Fabio Anzanello, Deli Huang, James Ricketts, Jonathan L. Torres, Nathan Beutler, Linghang Peng, Sirena Vargas, Jon Cassell, Mara Parren, Linlin Yang, Caroline Ignacio, Davey M Smith, James E. Voss, David Nemazee, Andrew B. Ward, Thomas Rogers, Dennis R. Burton, Raiees Andrabi

Posted 23 Sep 2020
bioRxiv DOI: 10.1101/2020.09.22.308965

Pre-existing immune responses to seasonal endemic coronaviruses could have profound consequences for antibody responses to SARS-CoV-2, either induced in natural infection or through vaccination. Such consequences are well established in the influenza and flavivirus fields. A first step to establish whether pre-existing responses can impact SARS-CoV-2 infection is to understand the nature and extent of cross-reactivity in humans to coronaviruses. We compared serum antibody and memory B cell responses to coronavirus spike (S) proteins from pre-pandemic and SARS-CoV-2 convalescent donors using a series of binding and functional assays. We found weak evidence of pre-existing SARS-CoV-2 cross-reactive serum antibodies in pre-pandemic donors. However, we found stronger evidence of pre-existing cross-reactive memory B cells that were activated on SARS-CoV-2 infection. Monoclonal antibodies (mAbs) isolated from the donors showed varying degrees of cross-reactivity with betacoronaviruses, including SARS and endemic coronaviruses. None of the cross-reactive mAbs were neutralizing except for one that targeted the S2 subunit of the S protein. The results suggest that pre-existing immunity to endemic coronaviruses should be considered in evaluating antibody responses to SARS-CoV-2. ### Competing Interest Statement R.A., G.S., W.H., T.F.R., and D.R.B. are listed as inventors on pending patent applications describing the SARS-CoV-2 and HCoV-HKU1 cross-reactive antibodies. D.R.B. is a consultant for IAVI. All other authors have no competing interests to declare.

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