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A single BNT162b2 mRNA dose elicits antibodies with Fc-mediated effector functions and boost pre-existing humoral and T cell responses

Alexandra Tauzin, Manon Nayrac, Mehdi Benlarbi, Shang Yu Gong, Romain Gasser, Guillaume Beaudoin-Bussières, Nathalie Brassard, Annemarie Laumaea, Dani Vézina, Jérémie Prévost, Sai Priya Anand, Catherine Bourassa, Gabrielle Gendron-Lepage, Halima Medjahed, Guillaume Goyette, Julia Niessl, Olivier Tastet, Laurie Gokool, Chantal Morrisseau, Pascale Arlotto, Leonidas Stamatatos, Andrew T. McGuire, Catherine Larochelle, Pradeep Uchil, Maolin Lu, Walther Mothes, Gaston De Serres, Sandrine Moreira, Michel Roger, Jonathan Richard, Valérie Martel-Laferrière, Ralf Duerr, Cécile Tremblay, Daniel E. Kaufmann, Andrés Finzi
doi: https://doi.org/10.1101/2021.03.18.435972
Alexandra Tauzin
1Centre de Recherche du CHUM, Montréal, QC, Canada
2Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada
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Manon Nayrac
1Centre de Recherche du CHUM, Montréal, QC, Canada
2Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada
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Mehdi Benlarbi
1Centre de Recherche du CHUM, Montréal, QC, Canada
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Shang Yu Gong
1Centre de Recherche du CHUM, Montréal, QC, Canada
3Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada
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Romain Gasser
1Centre de Recherche du CHUM, Montréal, QC, Canada
2Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada
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Guillaume Beaudoin-Bussières
1Centre de Recherche du CHUM, Montréal, QC, Canada
2Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada
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Nathalie Brassard
1Centre de Recherche du CHUM, Montréal, QC, Canada
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Annemarie Laumaea
1Centre de Recherche du CHUM, Montréal, QC, Canada
2Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada
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Dani Vézina
1Centre de Recherche du CHUM, Montréal, QC, Canada
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Jérémie Prévost
1Centre de Recherche du CHUM, Montréal, QC, Canada
2Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada
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Sai Priya Anand
1Centre de Recherche du CHUM, Montréal, QC, Canada
3Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada
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Catherine Bourassa
1Centre de Recherche du CHUM, Montréal, QC, Canada
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Gabrielle Gendron-Lepage
1Centre de Recherche du CHUM, Montréal, QC, Canada
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Halima Medjahed
1Centre de Recherche du CHUM, Montréal, QC, Canada
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Guillaume Goyette
1Centre de Recherche du CHUM, Montréal, QC, Canada
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Julia Niessl
1Centre de Recherche du CHUM, Montréal, QC, Canada
2Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada
12Consortium for HIV/AIDS Vaccine Development (CHAVD), La Jolla, CA, USA
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Olivier Tastet
1Centre de Recherche du CHUM, Montréal, QC, Canada
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Laurie Gokool
1Centre de Recherche du CHUM, Montréal, QC, Canada
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Chantal Morrisseau
1Centre de Recherche du CHUM, Montréal, QC, Canada
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Pascale Arlotto
1Centre de Recherche du CHUM, Montréal, QC, Canada
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Leonidas Stamatatos
4Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, WA, USA
5University of Washington, Department of Global Health, Seattle, WA 98109, USA
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Andrew T. McGuire
4Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, WA, USA
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Catherine Larochelle
1Centre de Recherche du CHUM, Montréal, QC, Canada
6Département des Neurosciences, Université de Montréal, Montreal, QC, Canada
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Pradeep Uchil
7Department of Microbial Pathogenesis, School of Medicine, New Haven, CT, USA
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Maolin Lu
7Department of Microbial Pathogenesis, School of Medicine, New Haven, CT, USA
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Walther Mothes
7Department of Microbial Pathogenesis, School of Medicine, New Haven, CT, USA
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Gaston De Serres
8Institut National de Santé Publique du Québec, Quebec, QC, Canada
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Sandrine Moreira
9Laboratoire de Santé Publique du Québec, Institut national de santé publique du Québec, Sainte-Anne-de-Bellevue, QC, Canada
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Michel Roger
1Centre de Recherche du CHUM, Montréal, QC, Canada
2Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada
9Laboratoire de Santé Publique du Québec, Institut national de santé publique du Québec, Sainte-Anne-de-Bellevue, QC, Canada
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Jonathan Richard
1Centre de Recherche du CHUM, Montréal, QC, Canada
2Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada
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Valérie Martel-Laferrière
1Centre de Recherche du CHUM, Montréal, QC, Canada
2Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada
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Ralf Duerr
10Department of Microbiology, New York University School of Medicine, New York, NY, USA
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Cécile Tremblay
1Centre de Recherche du CHUM, Montréal, QC, Canada
2Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada
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  • For correspondence: c.tremblay@umontreal.ca daniel.kaufmann@umontreal.ca andres.finzi@umontreal.ca
Daniel E. Kaufmann
1Centre de Recherche du CHUM, Montréal, QC, Canada
11Département de Médecine, Université de Montréal, Montreal, QC, Canada
12Consortium for HIV/AIDS Vaccine Development (CHAVD), La Jolla, CA, USA
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  • For correspondence: c.tremblay@umontreal.ca daniel.kaufmann@umontreal.ca andres.finzi@umontreal.ca
Andrés Finzi
1Centre de Recherche du CHUM, Montréal, QC, Canada
2Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC, Canada
3Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada
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  • For correspondence: c.tremblay@umontreal.ca daniel.kaufmann@umontreal.ca andres.finzi@umontreal.ca
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Abstract

The standard dosing of the Pfizer/BioNTech BNT162b2 mRNA vaccine validated in clinical trials includes two doses administered three weeks apart. While the decision by some public health authorities to space the doses because of limiting supply has raised concerns about vaccine efficacy, data indicate that a single dose is up to 90% effective starting 14 days after its administration. We analyzed humoral and T cells responses three weeks after a single dose of this mRNA vaccine. Despite the proven efficacy of the vaccine at this time point, no neutralizing activity were elicited in SARS-CoV-2 naïve individuals. However, we detected strong anti-receptor binding domain (RBD) and Spike antibodies with Fc-mediated effector functions and cellular responses dominated by the CD4+ T cell component. A single dose of this mRNA vaccine to individuals previously infected by SARS-CoV-2 boosted all humoral and T cell responses measured, with strong correlations between T helper and antibody immunity. Neutralizing responses were increased in both potency and breadth, with distinctive capacity to neutralize emerging variant strains. Our results highlight the importance of vaccinating uninfected and previously-infected individuals and shed new light into the potential role of Fc-mediated effector functions and T cell responses in vaccine efficacy. They also provide support to spacing the doses of two-vaccine regimens to vaccinate a larger pool of the population in the context of vaccine scarcity against SARS-CoV-2.

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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A single BNT162b2 mRNA dose elicits antibodies with Fc-mediated effector functions and boost pre-existing humoral and T cell responses
Alexandra Tauzin, Manon Nayrac, Mehdi Benlarbi, Shang Yu Gong, Romain Gasser, Guillaume Beaudoin-Bussières, Nathalie Brassard, Annemarie Laumaea, Dani Vézina, Jérémie Prévost, Sai Priya Anand, Catherine Bourassa, Gabrielle Gendron-Lepage, Halima Medjahed, Guillaume Goyette, Julia Niessl, Olivier Tastet, Laurie Gokool, Chantal Morrisseau, Pascale Arlotto, Leonidas Stamatatos, Andrew T. McGuire, Catherine Larochelle, Pradeep Uchil, Maolin Lu, Walther Mothes, Gaston De Serres, Sandrine Moreira, Michel Roger, Jonathan Richard, Valérie Martel-Laferrière, Ralf Duerr, Cécile Tremblay, Daniel E. Kaufmann, Andrés Finzi
bioRxiv 2021.03.18.435972; doi: https://doi.org/10.1101/2021.03.18.435972
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A single BNT162b2 mRNA dose elicits antibodies with Fc-mediated effector functions and boost pre-existing humoral and T cell responses
Alexandra Tauzin, Manon Nayrac, Mehdi Benlarbi, Shang Yu Gong, Romain Gasser, Guillaume Beaudoin-Bussières, Nathalie Brassard, Annemarie Laumaea, Dani Vézina, Jérémie Prévost, Sai Priya Anand, Catherine Bourassa, Gabrielle Gendron-Lepage, Halima Medjahed, Guillaume Goyette, Julia Niessl, Olivier Tastet, Laurie Gokool, Chantal Morrisseau, Pascale Arlotto, Leonidas Stamatatos, Andrew T. McGuire, Catherine Larochelle, Pradeep Uchil, Maolin Lu, Walther Mothes, Gaston De Serres, Sandrine Moreira, Michel Roger, Jonathan Richard, Valérie Martel-Laferrière, Ralf Duerr, Cécile Tremblay, Daniel E. Kaufmann, Andrés Finzi
bioRxiv 2021.03.18.435972; doi: https://doi.org/10.1101/2021.03.18.435972

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