A single mRNA vaccine dose in COVID-19 patients boosts neutralizing antibodies against SARS-CoV-2 and variants of concern

RECoVERED Study Group

doi:10.1016/j.xcrm.2021.100486

A single mRNA vaccine dose in COVID-19 patients boosts neutralizing antibodies against SARS-CoV-2 and variants of concern

RECoVERED Study Group

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose-sparing strategies. Here, we evaluate the SARS-CoV-2-specific antibody responses following BNT162b2 vaccination in 150 previously SARS-CoV-2-infected individuals from a population-based cohort. One week after first vaccine dose, spike protein antibody levels are 27-fold higher and neutralizing antibody titers 12-fold higher, exceeding titers of fully vaccinated SARS-CoV-2-naive controls, with minimal additional boosting after the second dose. Neutralizing antibody titers against four variants of concern increase after vaccination; however, overall neutralization breadth does not improve. Pre-vaccination neutralizing antibody titers and time since infection have the largest positive effect on titers following vaccination. COVID-19 severity and the presence of comorbidities have no discernible impact on vaccine response. In conclusion, a single dose of BNT162b2 vaccine up to 15 months after SARS-CoV-2 infection offers higher neutralizing antibody titers than 2 vaccine doses in SARS-CoV-2-naive individuals.

Original language	English
Article number	100486
Journal	Cell Reports Medicine
Volume	3
Issue number	1
DOIs	https://doi.org/10.1016/j.xcrm.2021.100486
Publication status	Published - 18 Jan 2022

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10.1016/j.xcrm.2021.100486

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@article{4bf023e986da40e0a504e6d3acdc2261,

title = "A single mRNA vaccine dose in COVID-19 patients boosts neutralizing antibodies against SARS-CoV-2 and variants of concern",

abstract = "The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose-sparing strategies. Here, we evaluate the SARS-CoV-2-specific antibody responses following BNT162b2 vaccination in 150 previously SARS-CoV-2-infected individuals from a population-based cohort. One week after first vaccine dose, spike protein antibody levels are 27-fold higher and neutralizing antibody titers 12-fold higher, exceeding titers of fully vaccinated SARS-CoV-2-naive controls, with minimal additional boosting after the second dose. Neutralizing antibody titers against four variants of concern increase after vaccination; however, overall neutralization breadth does not improve. Pre-vaccination neutralizing antibody titers and time since infection have the largest positive effect on titers following vaccination. COVID-19 severity and the presence of comorbidities have no discernible impact on vaccine response. In conclusion, a single dose of BNT162b2 vaccine up to 15 months after SARS-CoV-2 infection offers higher neutralizing antibody titers than 2 vaccine doses in SARS-CoV-2-naive individuals.",

keywords = "antibody response, BNT162b2, COVID-19, mRNA vaccine, neutralization, previous infection, response predictors, SARS-CoV-2, variants",

author = "{van Gils}, {Marit J.} and {van Willigen}, {Hugo D.G.} and Elke Wynberg and Han, {Alvin X.} and {van der Straten}, Karlijn and Burger, {Judith A.} and Meliawati Poniman and Melissa Oomen and Khadija Tejjani and Bouhuijs, {Joey H.} and Anouk Verveen and Romy Lebbink and Maartje Dijkstra and Brent Appelman and Lavell, {A. H.Ayesha} and Caniels, {Tom G.} and Ilja Bontjer and {van Vught}, {Lonneke A.} and Vlaar, {Alexander P.J.} and Sikkens, {Jonne J.} and Bomers, {Marije K.} and Russell, {Colin A.} and Kootstra, {Neeltje A.} and Sanders, {Rogier W.} and Maria Prins and {de Bree}, {Godelieve J.} and {de Jong}, {Menno D.} and Ivette Agard and Jane Ayal and Anders Boyd and Floor Cavdar and Marianne Craanen and Udi Davidovich and Annemarieke Deuring and {van Dijk}, Annelies and Ertan Ersan and {del Grande}, Laura and Joost Hartman and Nelleke Koedoot and Tjalling Leenstra and Dominique Loomans and Agata Makowska and {du Maine}, Tom and {de Man}, Ilja and Amy Matser and {van der Meij}, Lizenka and {van Polanen}, Marleen and Maria Oud and Clark Reid and Leeann Storey and {de Wit}, Marije and {van Wijk}, Marc and {van Assem}, Joyce and {van den Aardweg}, Joost and {van Beek}, Marijne and Thyra Blankert and Brigitte Boeser-Nunnink and {Moll van Charante}, Eric and {van Dort}, Karel and Orlane Figaroa and Leah Frenkel and Arginell Girigorie and {van Haga}, Jelle and Agnes Harskamp-Holwerda and Mette Hazenberg and Soemeja Hidad and {de Jong}, Nina and Marcel Jonges and Suzanne Jurriaans and Hans Knoop and Lara Kuijt and Anja Lok and Ruiz, {Marga Mangas} and Irma Maurer and Pythia Nieuwkerk and {van Nuenen}, Ad and {van der Veen}, Annelou and Bas Verkaik and Visser, {Gerben Rienk} and {RECoVERED Study Group}",

note = "Funding Information: The authors wish to thank all RECoVERED and S3 study participants; Mathieu A.F. Claireaux of Amsterdam UMC, Amsterdam, the Netherlands, for providing the control proteins; Dirk Eggink and Chantal Reusken of the National Institute for Public Health and the Environment, Bilthoven, the Netherlands, for providing the SARS-CoV-2 B.1.617.2 S protein; Gestur Vidarsson and Federica Linty of Sanquin, Amsterdam, the Netherlands, for providing the SARS-CoV-2 nucleocapsid protein; Dr. Paul Bieniasz and Theodora Hatziioannou of the Howard Hughes Medical Institute, Rockefeller University, New York, NY, USA, and Dr. Beatrice Hahn of the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA, for donating cells and reagents for pseudovirus neutralization assays; Mohamed Hoesein, Marco Hol, Melvin Angelovski, and their team at the Public Health Service of Amsterdam, Amsterdam, the Netherlands, for valuable logistical support of the vaccine study; and the Amsterdam UMC COVID-19 S3/HCW study group (D. van de Beek, M.C. Brouwer, D.T.P. Buis, N. Chekrouni, N. van Mourik, S.E. Olie, E.J.G. Peters, T.D.Y. Reijnders, M. Schinkel, M.A. Slim, and W.J. Wiersinga). This work was supported by the Netherlands Organization for Scientific Research (NWO) ZonMw (RECoVERED, grant agreement no. 10150062010002 , to M.D.d.J., the S3 study , grant agreement no. 10430022010023 , to M.K.B., and Vici grant no. 91818627 , to R.W.S.), the Bill and Melinda Gates Foundation (grant nos. INV-002022 and INV008818 , to R.W.S., and INV-024617 , to M.J.v.G.), Amsterdam UMC through the AMC Fellowship (to M.J.v.G.) and the Corona Research Fund (to M.K.B.), the European Research Council (no. 818353 , to C.A.R.), the European Union{\textquoteright}s Horizon 2020 program (RECoVER, grant no. 101003589 , to M.D.d.J.), and the Public Health Service of Amsterdam (Research & Development grant no. 21-14 , to M.P.). The funders had no role in study design, data collection, data analysis, data interpretation, or data reporting. Funding Information: The authors wish to thank all RECoVERED and S3 study participants; Mathieu A.F. Claireaux of Amsterdam UMC, Amsterdam, the Netherlands, for providing the control proteins; Dirk Eggink and Chantal Reusken of the National Institute for Public Health and the Environment, Bilthoven, the Netherlands, for providing the SARS-CoV-2 B.1.617.2 S protein; Gestur Vidarsson and Federica Linty of Sanquin, Amsterdam, the Netherlands, for providing the SARS-CoV-2 nucleocapsid protein; Dr. Paul Bieniasz and Theodora Hatziioannou of the Howard Hughes Medical Institute, Rockefeller University, New York, NY, USA, and Dr. Beatrice Hahn of the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA, for donating cells and reagents for pseudovirus neutralization assays; Mohamed Hoesein, Marco Hol, Melvin Angelovski, and their team at the Public Health Service of Amsterdam, Amsterdam, the Netherlands, for valuable logistical support of the vaccine study; and the Amsterdam UMC COVID-19 S3/HCW study group (D. van de Beek, M.C. Brouwer, D.T.P. Buis, N. Chekrouni, N. van Mourik, S.E. Olie, E.J.G. Peters, T.D.Y. Reijnders, M. Schinkel, M.A. Slim, and W.J. Wiersinga). This work was supported by the Netherlands Organization for Scientific Research (NWO) ZonMw (RECoVERED, grant agreement no. 10150062010002, to M.D.d.J. the S3 study, grant agreement no. 10430022010023, to M.K.B. and Vici grant no. 91818627, to R.W.S.), the Bill and Melinda Gates Foundation (grant nos. INV-002022 and INV008818, to R.W.S. and INV-024617, to M.J.v.G.), Amsterdam UMC through the AMC Fellowship (to M.J.v.G.) and the Corona Research Fund (to M.K.B.), the European Research Council (no. 818353, to C.A.R.), the European Union's Horizon 2020 program (RECoVER, grant no. 101003589, to M.D.d.J.), and the Public Health Service of Amsterdam (Research & Development grant no. 21-14, to M.P.). The funders had no role in study design, data collection, data analysis, data interpretation, or data reporting. Conceptualization, M.J.v.G. C.A.R. M. Prins, G.J.d.B. and M.D.d.J.; funding acquisition, M.J.v.G. A.X.H. J.J.S. R.W.S. C.A.R. M. Prins, and M.D.d.J.; investigation, H.D.G.v.W. E.W. K.v.d.S. J.A.B. M.O. K.T. M. Poniman, and J.H.B.; methodology, M.J.v.G. H.D.G.v.W. E.W. A.X.H. K.v.d.S. R.W.S. C.A.R. M. Prins, G.J.d.B. and M.D.d.J.; project administration, H.D.G.v.W. E.W. N.A.K. M. Prins, G.J.d.B. and M.D.d.J.; resources, H.D.G.v.W. E.W. A.V. R.L. M.D. J.A.B. M.O. K.T. M. Poniman, J.H.B. B.A. A.H.A.L. T.G.C. I.B. L.A.v.V. A.P.J.V. J.J.S. M.K.B. R.W.S. and the RECoVERED Study Group; data analysis, M.J.v.G. A.X.H. K.v.d.S. and M. Poniman; supervision, M.J.v.G. A.P.J.V. J.J.S. M.K.B. N.A.K. C.A.R. M. Prins. G.J.d.B. and M.D.d.J.; writing ? original draft, M.J.v.G. A.X.H. C.A.R. and M.D.d.J.; writing ? review & editing, all authors. The authors declare no competing interests. We worked to ensure gender balance in the recruitment of human subjects. We worked to ensure ethnic or other types of diversity in the recruitment of human subjects. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this article self-identifies as a member of the LGBTQ+ community. The author list of this article includes contributors from the location where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. Publisher Copyright: {\textcopyright} 2021",

year = "2022",

month = jan,

day = "18",

doi = "10.1016/j.xcrm.2021.100486",

language = "English",

volume = "3",

journal = "Cell reports. Medicine",

issn = "2666-3791",

publisher = "Cell Press",

number = "1",

}

TY - JOUR

T1 - A single mRNA vaccine dose in COVID-19 patients boosts neutralizing antibodies against SARS-CoV-2 and variants of concern

AU - van Gils, Marit J.

AU - van Willigen, Hugo D.G.

AU - Wynberg, Elke

AU - Han, Alvin X.

AU - van der Straten, Karlijn

AU - Burger, Judith A.

AU - Poniman, Meliawati

AU - Oomen, Melissa

AU - Tejjani, Khadija

AU - Bouhuijs, Joey H.

AU - Verveen, Anouk

AU - Lebbink, Romy

AU - Dijkstra, Maartje

AU - Appelman, Brent

AU - Lavell, A. H.Ayesha

AU - Caniels, Tom G.

AU - Bontjer, Ilja

AU - van Vught, Lonneke A.

AU - Vlaar, Alexander P.J.

AU - Sikkens, Jonne J.

AU - Bomers, Marije K.

AU - Russell, Colin A.

AU - Kootstra, Neeltje A.

AU - Sanders, Rogier W.

AU - Prins, Maria

AU - de Bree, Godelieve J.

AU - de Jong, Menno D.

AU - Agard, Ivette

AU - Ayal, Jane

AU - Boyd, Anders

AU - Cavdar, Floor

AU - Craanen, Marianne

AU - Davidovich, Udi

AU - Deuring, Annemarieke

AU - van Dijk, Annelies

AU - Ersan, Ertan

AU - del Grande, Laura

AU - Hartman, Joost

AU - Koedoot, Nelleke

AU - Leenstra, Tjalling

AU - Loomans, Dominique

AU - Makowska, Agata

AU - du Maine, Tom

AU - de Man, Ilja

AU - Matser, Amy

AU - van der Meij, Lizenka

AU - van Polanen, Marleen

AU - Oud, Maria

AU - Reid, Clark

AU - Storey, Leeann

AU - de Wit, Marije

AU - van Wijk, Marc

AU - van Assem, Joyce

AU - van den Aardweg, Joost

AU - van Beek, Marijne

AU - Blankert, Thyra

AU - Boeser-Nunnink, Brigitte

AU - Moll van Charante, Eric

AU - van Dort, Karel

AU - Figaroa, Orlane

AU - Frenkel, Leah

AU - Girigorie, Arginell

AU - van Haga, Jelle

AU - Harskamp-Holwerda, Agnes

AU - Hazenberg, Mette

AU - Hidad, Soemeja

AU - de Jong, Nina

AU - Jonges, Marcel

AU - Jurriaans, Suzanne

AU - Knoop, Hans

AU - Kuijt, Lara

AU - Lok, Anja

AU - Ruiz, Marga Mangas

AU - Maurer, Irma

AU - Nieuwkerk, Pythia

AU - van Nuenen, Ad

AU - van der Veen, Annelou

AU - Verkaik, Bas

AU - Visser, Gerben Rienk

AU - RECoVERED Study Group

N1 - Funding Information: The authors wish to thank all RECoVERED and S3 study participants; Mathieu A.F. Claireaux of Amsterdam UMC, Amsterdam, the Netherlands, for providing the control proteins; Dirk Eggink and Chantal Reusken of the National Institute for Public Health and the Environment, Bilthoven, the Netherlands, for providing the SARS-CoV-2 B.1.617.2 S protein; Gestur Vidarsson and Federica Linty of Sanquin, Amsterdam, the Netherlands, for providing the SARS-CoV-2 nucleocapsid protein; Dr. Paul Bieniasz and Theodora Hatziioannou of the Howard Hughes Medical Institute, Rockefeller University, New York, NY, USA, and Dr. Beatrice Hahn of the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA, for donating cells and reagents for pseudovirus neutralization assays; Mohamed Hoesein, Marco Hol, Melvin Angelovski, and their team at the Public Health Service of Amsterdam, Amsterdam, the Netherlands, for valuable logistical support of the vaccine study; and the Amsterdam UMC COVID-19 S3/HCW study group (D. van de Beek, M.C. Brouwer, D.T.P. Buis, N. Chekrouni, N. van Mourik, S.E. Olie, E.J.G. Peters, T.D.Y. Reijnders, M. Schinkel, M.A. Slim, and W.J. Wiersinga). This work was supported by the Netherlands Organization for Scientific Research (NWO) ZonMw (RECoVERED, grant agreement no. 10150062010002 , to M.D.d.J., the S3 study , grant agreement no. 10430022010023 , to M.K.B., and Vici grant no. 91818627 , to R.W.S.), the Bill and Melinda Gates Foundation (grant nos. INV-002022 and INV008818 , to R.W.S., and INV-024617 , to M.J.v.G.), Amsterdam UMC through the AMC Fellowship (to M.J.v.G.) and the Corona Research Fund (to M.K.B.), the European Research Council (no. 818353 , to C.A.R.), the European Union’s Horizon 2020 program (RECoVER, grant no. 101003589 , to M.D.d.J.), and the Public Health Service of Amsterdam (Research & Development grant no. 21-14 , to M.P.). The funders had no role in study design, data collection, data analysis, data interpretation, or data reporting. Funding Information: The authors wish to thank all RECoVERED and S3 study participants; Mathieu A.F. Claireaux of Amsterdam UMC, Amsterdam, the Netherlands, for providing the control proteins; Dirk Eggink and Chantal Reusken of the National Institute for Public Health and the Environment, Bilthoven, the Netherlands, for providing the SARS-CoV-2 B.1.617.2 S protein; Gestur Vidarsson and Federica Linty of Sanquin, Amsterdam, the Netherlands, for providing the SARS-CoV-2 nucleocapsid protein; Dr. Paul Bieniasz and Theodora Hatziioannou of the Howard Hughes Medical Institute, Rockefeller University, New York, NY, USA, and Dr. Beatrice Hahn of the Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA, for donating cells and reagents for pseudovirus neutralization assays; Mohamed Hoesein, Marco Hol, Melvin Angelovski, and their team at the Public Health Service of Amsterdam, Amsterdam, the Netherlands, for valuable logistical support of the vaccine study; and the Amsterdam UMC COVID-19 S3/HCW study group (D. van de Beek, M.C. Brouwer, D.T.P. Buis, N. Chekrouni, N. van Mourik, S.E. Olie, E.J.G. Peters, T.D.Y. Reijnders, M. Schinkel, M.A. Slim, and W.J. Wiersinga). This work was supported by the Netherlands Organization for Scientific Research (NWO) ZonMw (RECoVERED, grant agreement no. 10150062010002, to M.D.d.J. the S3 study, grant agreement no. 10430022010023, to M.K.B. and Vici grant no. 91818627, to R.W.S.), the Bill and Melinda Gates Foundation (grant nos. INV-002022 and INV008818, to R.W.S. and INV-024617, to M.J.v.G.), Amsterdam UMC through the AMC Fellowship (to M.J.v.G.) and the Corona Research Fund (to M.K.B.), the European Research Council (no. 818353, to C.A.R.), the European Union's Horizon 2020 program (RECoVER, grant no. 101003589, to M.D.d.J.), and the Public Health Service of Amsterdam (Research & Development grant no. 21-14, to M.P.). The funders had no role in study design, data collection, data analysis, data interpretation, or data reporting. Conceptualization, M.J.v.G. C.A.R. M. Prins, G.J.d.B. and M.D.d.J.; funding acquisition, M.J.v.G. A.X.H. J.J.S. R.W.S. C.A.R. M. Prins, and M.D.d.J.; investigation, H.D.G.v.W. E.W. K.v.d.S. J.A.B. M.O. K.T. M. Poniman, and J.H.B.; methodology, M.J.v.G. H.D.G.v.W. E.W. A.X.H. K.v.d.S. R.W.S. C.A.R. M. Prins, G.J.d.B. and M.D.d.J.; project administration, H.D.G.v.W. E.W. N.A.K. M. Prins, G.J.d.B. and M.D.d.J.; resources, H.D.G.v.W. E.W. A.V. R.L. M.D. J.A.B. M.O. K.T. M. Poniman, J.H.B. B.A. A.H.A.L. T.G.C. I.B. L.A.v.V. A.P.J.V. J.J.S. M.K.B. R.W.S. and the RECoVERED Study Group; data analysis, M.J.v.G. A.X.H. K.v.d.S. and M. Poniman; supervision, M.J.v.G. A.P.J.V. J.J.S. M.K.B. N.A.K. C.A.R. M. Prins. G.J.d.B. and M.D.d.J.; writing ? original draft, M.J.v.G. A.X.H. C.A.R. and M.D.d.J.; writing ? review & editing, all authors. The authors declare no competing interests. We worked to ensure gender balance in the recruitment of human subjects. We worked to ensure ethnic or other types of diversity in the recruitment of human subjects. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this article self-identifies as a member of the LGBTQ+ community. The author list of this article includes contributors from the location where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. Publisher Copyright: © 2021

PY - 2022/1/18

Y1 - 2022/1/18

N2 - The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose-sparing strategies. Here, we evaluate the SARS-CoV-2-specific antibody responses following BNT162b2 vaccination in 150 previously SARS-CoV-2-infected individuals from a population-based cohort. One week after first vaccine dose, spike protein antibody levels are 27-fold higher and neutralizing antibody titers 12-fold higher, exceeding titers of fully vaccinated SARS-CoV-2-naive controls, with minimal additional boosting after the second dose. Neutralizing antibody titers against four variants of concern increase after vaccination; however, overall neutralization breadth does not improve. Pre-vaccination neutralizing antibody titers and time since infection have the largest positive effect on titers following vaccination. COVID-19 severity and the presence of comorbidities have no discernible impact on vaccine response. In conclusion, a single dose of BNT162b2 vaccine up to 15 months after SARS-CoV-2 infection offers higher neutralizing antibody titers than 2 vaccine doses in SARS-CoV-2-naive individuals.

AB - The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose-sparing strategies. Here, we evaluate the SARS-CoV-2-specific antibody responses following BNT162b2 vaccination in 150 previously SARS-CoV-2-infected individuals from a population-based cohort. One week after first vaccine dose, spike protein antibody levels are 27-fold higher and neutralizing antibody titers 12-fold higher, exceeding titers of fully vaccinated SARS-CoV-2-naive controls, with minimal additional boosting after the second dose. Neutralizing antibody titers against four variants of concern increase after vaccination; however, overall neutralization breadth does not improve. Pre-vaccination neutralizing antibody titers and time since infection have the largest positive effect on titers following vaccination. COVID-19 severity and the presence of comorbidities have no discernible impact on vaccine response. In conclusion, a single dose of BNT162b2 vaccine up to 15 months after SARS-CoV-2 infection offers higher neutralizing antibody titers than 2 vaccine doses in SARS-CoV-2-naive individuals.

KW - antibody response

KW - BNT162b2

KW - COVID-19

KW - mRNA vaccine

KW - neutralization

KW - previous infection

KW - response predictors

KW - SARS-CoV-2

KW - variants

UR - http://www.scopus.com/inward/record.url?scp=85122015551&partnerID=8YFLogxK

U2 - 10.1016/j.xcrm.2021.100486

DO - 10.1016/j.xcrm.2021.100486

M3 - Article

C2 - 35103254

AN - SCOPUS:85122015551

SN - 2666-3791

VL - 3

JO - Cell reports. Medicine

JF - Cell reports. Medicine

IS - 1

M1 - 100486

ER -

A single mRNA vaccine dose in COVID-19 patients boosts neutralizing antibodies against SARS-CoV-2 and variants of concern

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