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Subtle immunological differences in mRNA-1273 and BNT162b2 COVID-19 vaccine induced Fc-functional profiles

Paulina Kaplonek, Deniz Cizmeci, Stephanie Fischinger, Ai-ris Collier, Todd Suscovich, Caitlyn Linde, Thomas Broge, Colin Mann, Fatima Amanat, Diana Dayal, Justin Rhee, Michael de St. Aubin, Eric J. Nilles, Elon R. Musk, Anil S. Menon, Erica Ollmann Saphire, Florian Krammer, Douglas A. Lauffenburger, Dan H. Barouch, Galit Alter
doi: https://doi.org/10.1101/2021.08.31.458247
Paulina Kaplonek
1Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
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Deniz Cizmeci
1Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
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Stephanie Fischinger
1Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
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Ai-ris Collier
2Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
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Todd Suscovich
3Seromyx Systems Inc, Cambridge, MA, USA
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Caitlyn Linde
3Seromyx Systems Inc, Cambridge, MA, USA
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Thomas Broge
3Seromyx Systems Inc, Cambridge, MA, USA
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Colin Mann
4Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla Institute for Immunology, La Jolla, CA, USA
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Fatima Amanat
5Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Diana Dayal
6Space Exploration Technologies Corp, Hawthorne, CA, USA
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Justin Rhee
6Space Exploration Technologies Corp, Hawthorne, CA, USA
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Michael de St. Aubin
7Brigham Women’s Hospital, Boston, MA, USA
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Eric J. Nilles
7Brigham Women’s Hospital, Boston, MA, USA
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Elon R. Musk
6Space Exploration Technologies Corp, Hawthorne, CA, USA
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Anil S. Menon
6Space Exploration Technologies Corp, Hawthorne, CA, USA
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Erica Ollmann Saphire
4Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla Institute for Immunology, La Jolla, CA, USA
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Florian Krammer
5Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Douglas A. Lauffenburger
8Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
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Dan H. Barouch
1Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
2Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
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Galit Alter
1Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA
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  • For correspondence: alter@mgh.harvard.edu
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Abstract

The successful development of several COVID-19 vaccines has substantially reduced morbidity and mortality in regions of the world where the vaccines have been deployed. However, in the wake of the emergence of viral variants, able to evade vaccine induced neutralizing antibodies, real world vaccine efficacy has begun to show differences across the mRNA platforms, suggesting that subtle variation in immune responses induced by the BNT162b2 and mRNA1273 vaccines may provide differential protection. Given our emerging appreciation for the importance of additional antibody functions, beyond neutralization, here we profiled the postboost binding and functional capacity of the humoral response induced by the BNT162b2 and mRNA-1273 in a cohort of hospital staff. Both vaccines induced robust humoral immune responses to WT SARS-CoV-2 and VOCs. However, differences emerged across epitopespecific responses, with higher RBD- and NTD-specific IgA, as well as functional antibodies (ADNP and ADNK) in mRNA-1273 vaccine recipients. Additionally, RBD-specific antibody depletion highlighted the different roles of non-RBD-specific antibody effector function induced across the mRNA vaccines, providing novel insights into potential differences in protective immunity generated across these vaccines in the setting of newly emerging VOCs.

Competing Interest Statement

G.A. is a founder and equity holder for Seromyx Systems Inc., an employee and equity holder for Leyden Labs, and has received financial support from Abbvie, BioNtech, GSK, Gilead, Merck, Moderna, Novartis, Pfizer, and Sanofi. D.D., J.R., A.S.M, and E.R.M. are employees of Space Exploration Technologies Corp. All other authors have declared that no conflict of interest exists.

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-NC-ND 4.0 International license.
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Posted August 31, 2021.
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Subtle immunological differences in mRNA-1273 and BNT162b2 COVID-19 vaccine induced Fc-functional profiles
Paulina Kaplonek, Deniz Cizmeci, Stephanie Fischinger, Ai-ris Collier, Todd Suscovich, Caitlyn Linde, Thomas Broge, Colin Mann, Fatima Amanat, Diana Dayal, Justin Rhee, Michael de St. Aubin, Eric J. Nilles, Elon R. Musk, Anil S. Menon, Erica Ollmann Saphire, Florian Krammer, Douglas A. Lauffenburger, Dan H. Barouch, Galit Alter
bioRxiv 2021.08.31.458247; doi: https://doi.org/10.1101/2021.08.31.458247
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Subtle immunological differences in mRNA-1273 and BNT162b2 COVID-19 vaccine induced Fc-functional profiles
Paulina Kaplonek, Deniz Cizmeci, Stephanie Fischinger, Ai-ris Collier, Todd Suscovich, Caitlyn Linde, Thomas Broge, Colin Mann, Fatima Amanat, Diana Dayal, Justin Rhee, Michael de St. Aubin, Eric J. Nilles, Elon R. Musk, Anil S. Menon, Erica Ollmann Saphire, Florian Krammer, Douglas A. Lauffenburger, Dan H. Barouch, Galit Alter
bioRxiv 2021.08.31.458247; doi: https://doi.org/10.1101/2021.08.31.458247

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