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Determining the optimal SARS-CoV-2 mRNA vaccine dosing interval for maximum immunogenicity

View ORCID ProfileMichael Asamoah-Boaheng, View ORCID ProfileDavid M. Goldfarb, Martin A. Prusinkiewicz, Liam Golding, View ORCID ProfileMohammad Ehsanul Karim, Vilte Barakauskas, Nechelle Wall, Agatha N. Jassem, Ana Citlali Marquez, Chris MacDonald, View ORCID ProfileSheila F. O’Brien, View ORCID ProfilePascal Lavoie, View ORCID ProfileBrian Grunau
doi: https://doi.org/10.1101/2022.03.01.482592
Michael Asamoah-Boaheng
1Department of Emergency Medicine, University of British Columbia, Canada
2Faculty of Medicine, Clinical Epidemiology, Memorial University of Newfoundland, Canada
MPhil
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  • For correspondence: masamoahboah@mun.ca
David M. Goldfarb
3Department of Pathology and Laboratory Medicine, University of British Columbia, Canada
MD
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Martin A. Prusinkiewicz
4Department of Pediatrics, University of British Columbia, Canada
PhD
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Liam Golding
5Department of Obstetrics and Gynecology, University of British Columbia, Canada
BSc
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Mohammad Ehsanul Karim
6Centre for Health Evaluation & Outcome Sciences, University of British Columbia, Canada
7School of Population and Public Health, University of British Columbia, Canada
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Vilte Barakauskas
3Department of Pathology and Laboratory Medicine, University of British Columbia, Canada
PhD
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Nechelle Wall
8British Columbia Emergency Health Services, British Columbia, Canada
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Agatha N. Jassem
3Department of Pathology and Laboratory Medicine, University of British Columbia, Canada
9Public Health Laboratory, British Columbia Centre for Disease Control, British Columbia, Canada
PhD
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Ana Citlali Marquez
3Department of Pathology and Laboratory Medicine, University of British Columbia, Canada
9Public Health Laboratory, British Columbia Centre for Disease Control, British Columbia, Canada
PhD
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Chris MacDonald
10Dalla Lana School of Public Health, University of Toronto, Toronto, Canada
11Ontario Occupational Cancer Research Centre, Ontario, Canada
MScCH
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Sheila F. O’Brien
11Ontario Occupational Cancer Research Centre, Ontario, Canada
12School of Epidemiology & Public Health, Universtiy of Ottawa, Ottawa, Canada
PhD
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Pascal Lavoie
5Department of Obstetrics and Gynecology, University of British Columbia, Canada
MDCM, PhD
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Brian Grunau
1Department of Emergency Medicine, University of British Columbia, Canada
6Centre for Health Evaluation & Outcome Sciences, University of British Columbia, Canada
8British Columbia Emergency Health Services, British Columbia, Canada
MD MHSc
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ABSTRACT

Objective Emerging evidence indicates that longer SARS-CoV-2 vaccine dosing intervals results in an enhanced immune response. However, the optimal vaccine dosing interval for achieving maximum immunogenicity is unclear.

Methods This study included samples from adult paramedics in Canada who received two doses of either BNT162b2 or mRNA-1273 vaccines and provided blood samples 6 months (170 to 190 days) after the first vaccine dose. The main exposure variable was vaccine dosing interval (days), categorized as “short” (first quartile), “moderate” (second quartile), “long” (third quartile), and “longest” interval (fourth quartile). The primary outcome was total spike antibody concentrations, measured using the Elecsys SARS-CoV-2 total antibody assay. Secondary outcomes included: spike and RBD IgG antibody concentrations, and inhibition of angiotensin-converting enzyme 2 (ACE-2) binding to wild-type spike protein and several different Delta variant spike proteins. We fit a multiple log-linear regression model to investigate the association between vaccine dosing intervals and the antibody concentrations.

Results A total of 564 adult paramedics (mean age 40 years, SD=10) were included. Compared to “short interval” (≤30 days), higher dosing interval quartiles (moderate: 31-38 days; long: 39-73 days and longest: ≥74 days) were all associated with increased Elescys spike total antibody concentration. Compared to the short interval, “long” and “longest” interval quartiles were associated with higher spike and RBD IgG antibody concentrations. Similarly, increasing dosing intervals increased inhibition of ACE-2 binding to viral spike protein, regardless of the vaccine type.

Conclusion Increased mRNA vaccine dosing intervals longer than 30 days result in higher levels of circulating antibodies and viral neutralization when assessed at 6 months.

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 March 04, 2022.
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Determining the optimal SARS-CoV-2 mRNA vaccine dosing interval for maximum immunogenicity
Michael Asamoah-Boaheng, David M. Goldfarb, Martin A. Prusinkiewicz, Liam Golding, Mohammad Ehsanul Karim, Vilte Barakauskas, Nechelle Wall, Agatha N. Jassem, Ana Citlali Marquez, Chris MacDonald, Sheila F. O’Brien, Pascal Lavoie, Brian Grunau
bioRxiv 2022.03.01.482592; doi: https://doi.org/10.1101/2022.03.01.482592
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Determining the optimal SARS-CoV-2 mRNA vaccine dosing interval for maximum immunogenicity
Michael Asamoah-Boaheng, David M. Goldfarb, Martin A. Prusinkiewicz, Liam Golding, Mohammad Ehsanul Karim, Vilte Barakauskas, Nechelle Wall, Agatha N. Jassem, Ana Citlali Marquez, Chris MacDonald, Sheila F. O’Brien, Pascal Lavoie, Brian Grunau
bioRxiv 2022.03.01.482592; doi: https://doi.org/10.1101/2022.03.01.482592

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