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Engineered receptor binding domain immunogens elicit pan-coronavirus neutralizing antibodies

View ORCID ProfileBlake M. Hauser, Maya Sangesland, Evan C. Lam, Jared Feldman, Ashraf S. Yousif, Timothy M. Caradonna, View ORCID ProfileAlejandro B. Balazs, Daniel Lingwood, Aaron G. Schmidt
doi: https://doi.org/10.1101/2020.12.07.415216
Blake M. Hauser
1Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA
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  • ORCID record for Blake M. Hauser
Maya Sangesland
1Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA
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Evan C. Lam
1Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA
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Jared Feldman
1Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA
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Ashraf S. Yousif
1Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA
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Timothy M. Caradonna
1Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA
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Alejandro B. Balazs
1Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA
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  • ORCID record for Alejandro B. Balazs
Daniel Lingwood
1Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA
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  • For correspondence: dlingwood@mgh.harvard.edu aschmidt@crystal.harvard.edu
Aaron G. Schmidt
1Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, 02139, USA
2Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA
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Abstract

Effective countermeasures are needed against emerging coronaviruses of pandemic potential, similar to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Designing immunogens that elicit broadly neutralizing antibodies to conserved viral epitopes on the major surface glycoprotein, spike, such as the receptor binding domain (RBD) is one potential approach. Here, we report the generation of homotrimeric RBD immunogens from different sarbecoviruses using a stabilized, immune-silent trimerization tag. We find that that a cocktail of homotrimeric sarbecovirus RBDs can elicit a neutralizing response to all components even in context of prior SARS-CoV-2 imprinting. Importantly, the cross-neutralizing antibody responses are focused towards conserved RBD epitopes outside of the ACE-2 receptor-binding motif. This may be an effective strategy for eliciting broadly neutralizing responses leading to a pan-sarbecovirus vaccine.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted December 08, 2020.
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Engineered receptor binding domain immunogens elicit pan-coronavirus neutralizing antibodies
Blake M. Hauser, Maya Sangesland, Evan C. Lam, Jared Feldman, Ashraf S. Yousif, Timothy M. Caradonna, Alejandro B. Balazs, Daniel Lingwood, Aaron G. Schmidt
bioRxiv 2020.12.07.415216; doi: https://doi.org/10.1101/2020.12.07.415216
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Engineered receptor binding domain immunogens elicit pan-coronavirus neutralizing antibodies
Blake M. Hauser, Maya Sangesland, Evan C. Lam, Jared Feldman, Ashraf S. Yousif, Timothy M. Caradonna, Alejandro B. Balazs, Daniel Lingwood, Aaron G. Schmidt
bioRxiv 2020.12.07.415216; doi: https://doi.org/10.1101/2020.12.07.415216

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