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Driving potent neutralization of a SARS-CoV-2 Variant of Concern with a heterotypic boost

Daniel J. Sheward, Marco Mandolesi, Changil Kim, Leo Hanke, Laura Perez Vidakovics, Gerald McInerney, Gunilla B. Karlsson Hedestam, Ben Murrell
doi: https://doi.org/10.1101/2021.04.03.438330
Daniel J. Sheward
1Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
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  • For correspondence: daniel.sheward@ki.se gunilla.karlsson.hedestam@ki.se benjamin.murrell@ki.se
Marco Mandolesi
1Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
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Changil Kim
1Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
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Leo Hanke
1Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
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Laura Perez Vidakovics
1Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
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Gerald McInerney
1Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
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Gunilla B. Karlsson Hedestam
1Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
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  • For correspondence: daniel.sheward@ki.se gunilla.karlsson.hedestam@ki.se benjamin.murrell@ki.se
Ben Murrell
1Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
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  • For correspondence: daniel.sheward@ki.se gunilla.karlsson.hedestam@ki.se benjamin.murrell@ki.se
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Abstract

The emergence of SARS-CoV-2 Variants of Concern (VOCs) with mutations in key neutralizing antibody epitopes threatens to undermine vaccines developed against the pandemic founder variant (Wu-Hu-1). Widespread vaccine rollout and continued transmission are creating a population that has antibody responses of varying potency to Wu-Hu-1. Against this background, it is critical to assess the outcomes of subsequent booster vaccination with variant antigens. It is not yet known whether such heterotypic vaccine boosts would be compromised by original antigenic sin, where pre-existing responses to a prior variant dampen responses to a new one, or whether the primed memory B cell repertoire would bridge the gap between Wu-Hu-1 and VOCs. Here, we show that a single adjuvanted dose of receptor binding domain (RBD) protein from VOC 501Y.V2 (B.1.351) drives an extremely potent neutralizing antibody response capable of cross-neutralizing both Wu-Hu-1 and 501Y.V2 in rhesus macaques previously immunized with Wu-Hu-1 spike protein.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted April 05, 2021.
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Driving potent neutralization of a SARS-CoV-2 Variant of Concern with a heterotypic boost
Daniel J. Sheward, Marco Mandolesi, Changil Kim, Leo Hanke, Laura Perez Vidakovics, Gerald McInerney, Gunilla B. Karlsson Hedestam, Ben Murrell
bioRxiv 2021.04.03.438330; doi: https://doi.org/10.1101/2021.04.03.438330
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Driving potent neutralization of a SARS-CoV-2 Variant of Concern with a heterotypic boost
Daniel J. Sheward, Marco Mandolesi, Changil Kim, Leo Hanke, Laura Perez Vidakovics, Gerald McInerney, Gunilla B. Karlsson Hedestam, Ben Murrell
bioRxiv 2021.04.03.438330; doi: https://doi.org/10.1101/2021.04.03.438330

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