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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 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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