Beta RBD boost broadens antibody-mediated protection against SARS-CoV-2 variants in animal models

Summary: Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) with resistance to neutralizing antibodies are threatening to undermine vaccine efficacy. Vaccination and infection have led to widespread humoral immunity against the pandemic founder (Wu-Hu-1). Against...

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Autores principales: Daniel J. Sheward, Marco Mandolesi, Egon Urgard, Changil Kim, Leo Hanke, Laura Perez Vidakovics, Alec Pankow, Natalie L. Smith, Xaquin Castro Dopico, Gerald M. McInerney, Jonathan M. Coquet, Gunilla B. Karlsson Hedestam, Ben Murrell
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Publicado: Elsevier 2021
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Acceso en línea:https://doaj.org/article/f6fbb94e1aa445b28a40632a0756d791
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spelling oai:doaj.org-article:f6fbb94e1aa445b28a40632a0756d7912021-11-18T04:52:17ZBeta RBD boost broadens antibody-mediated protection against SARS-CoV-2 variants in animal models2666-379110.1016/j.xcrm.2021.100450https://doaj.org/article/f6fbb94e1aa445b28a40632a0756d7912021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2666379121003189https://doaj.org/toc/2666-3791Summary: Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) with resistance to neutralizing antibodies are threatening to undermine vaccine efficacy. Vaccination and infection have led to widespread humoral immunity against the pandemic founder (Wu-Hu-1). Against this background, it is critical to assess the outcomes of subsequent immunization with variant antigens. It is not yet clear whether heterotypic 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 memory B cell repertoire would bridge the gap between Wu-Hu-1 and VOCs. We show, in macaques immunized with Wu-Hu-1 spike, that a single dose of adjuvanted beta variant receptor binding domain (RBD) protein broadens neutralizing antibody responses to heterologous VOCs. Passive transfer of plasma sampled after Wu-Hu-1 spike immunization only partially protects K18-hACE2 mice from lethal challenge with a beta variant isolate, whereas plasma sampled following heterotypic RBD boost protects completely against disease.Daniel J. ShewardMarco MandolesiEgon UrgardChangil KimLeo HankeLaura Perez VidakovicsAlec PankowNatalie L. SmithXaquin Castro DopicoGerald M. McInerneyJonathan M. CoquetGunilla B. Karlsson HedestamBen MurrellElsevierarticleSARS-CoV-2variants of concernvaccinesoriginal antigenic sinheterotypic boostpassive immunizationMedicine (General)R5-920ENCell Reports Medicine, Vol 2, Iss 11, Pp 100450- (2021)
institution DOAJ
collection DOAJ
language EN
topic SARS-CoV-2
variants of concern
vaccines
original antigenic sin
heterotypic boost
passive immunization
Medicine (General)
R5-920
spellingShingle SARS-CoV-2
variants of concern
vaccines
original antigenic sin
heterotypic boost
passive immunization
Medicine (General)
R5-920
Daniel J. Sheward
Marco Mandolesi
Egon Urgard
Changil Kim
Leo Hanke
Laura Perez Vidakovics
Alec Pankow
Natalie L. Smith
Xaquin Castro Dopico
Gerald M. McInerney
Jonathan M. Coquet
Gunilla B. Karlsson Hedestam
Ben Murrell
Beta RBD boost broadens antibody-mediated protection against SARS-CoV-2 variants in animal models
description Summary: Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) with resistance to neutralizing antibodies are threatening to undermine vaccine efficacy. Vaccination and infection have led to widespread humoral immunity against the pandemic founder (Wu-Hu-1). Against this background, it is critical to assess the outcomes of subsequent immunization with variant antigens. It is not yet clear whether heterotypic 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 memory B cell repertoire would bridge the gap between Wu-Hu-1 and VOCs. We show, in macaques immunized with Wu-Hu-1 spike, that a single dose of adjuvanted beta variant receptor binding domain (RBD) protein broadens neutralizing antibody responses to heterologous VOCs. Passive transfer of plasma sampled after Wu-Hu-1 spike immunization only partially protects K18-hACE2 mice from lethal challenge with a beta variant isolate, whereas plasma sampled following heterotypic RBD boost protects completely against disease.
format article
author Daniel J. Sheward
Marco Mandolesi
Egon Urgard
Changil Kim
Leo Hanke
Laura Perez Vidakovics
Alec Pankow
Natalie L. Smith
Xaquin Castro Dopico
Gerald M. McInerney
Jonathan M. Coquet
Gunilla B. Karlsson Hedestam
Ben Murrell
author_facet Daniel J. Sheward
Marco Mandolesi
Egon Urgard
Changil Kim
Leo Hanke
Laura Perez Vidakovics
Alec Pankow
Natalie L. Smith
Xaquin Castro Dopico
Gerald M. McInerney
Jonathan M. Coquet
Gunilla B. Karlsson Hedestam
Ben Murrell
author_sort Daniel J. Sheward
title Beta RBD boost broadens antibody-mediated protection against SARS-CoV-2 variants in animal models
title_short Beta RBD boost broadens antibody-mediated protection against SARS-CoV-2 variants in animal models
title_full Beta RBD boost broadens antibody-mediated protection against SARS-CoV-2 variants in animal models
title_fullStr Beta RBD boost broadens antibody-mediated protection against SARS-CoV-2 variants in animal models
title_full_unstemmed Beta RBD boost broadens antibody-mediated protection against SARS-CoV-2 variants in animal models
title_sort beta rbd boost broadens antibody-mediated protection against sars-cov-2 variants in animal models
publisher Elsevier
publishDate 2021
url https://doaj.org/article/f6fbb94e1aa445b28a40632a0756d791
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