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Author Notes:

Galter@mgh.harvard.edu and rmedinai@uc.cl

Conceptualization, X.T., R.P.M., M.J.A., R.A.M., and G.A.; Methodology, X.T., R.P.M., and G.A; Validation, X.T.; Formal Analysis, X.T., R.P.M., and G.A.; Investigation, X.T., R.P.M., G.A., M.J.A. and R.A.M.; Cohort study design, supervised and managed the sample collection, T.G.S., C.P.R., A.R. and R.A.M.; Processed samples, revised the paper, T.G.S., C.P.R., J.L., E.P., E.S., A.M., A.R. and R.A.M.; Resources, G.A. and R.A.M.; Writing – Original Draft, X.T. and R.P.M.; Writing – Review & Editing, R.P.M., G.A., M.J.A. and R.A.M.; Visualization, X.T., R.P.M., and G.A.; Project Administration, R.P.M.; Funding Acquisition, G.A. and R.A.M.; Supervision, R.P.M., R.A.M. and G.A.

We would like to thank the laboratory of Prof. Douglas Lauffenburger (Massachusetts Institute of Technology) for the critical evaluation of statistics in this manuscript. We also thank Mark and Lisa Schwartz, Terry and Susan Ragon, and the SAMANA Kay MGH Research Scholars award for their support. G.A. receives funding from the Massachusetts Consortium on Pathogen Readiness (MassCPR), the Gates Global Health Vaccine Accelerator Platform, and the NIH (3R37AI080289-11S1, R01AI146785, U19AI42790-01, U19AI135995-02, U19AI42790-01, P01AI1650721, U01CA260476 - 01, CIVIC75N93019C00052).

We also would like to thank Estefany Poblete, Erick Salinas and Andres Muñoz for their excellent technical and professional expertise during clinical recruitment and sample processing.

Galit Alter is a founder/equity holder in Seroymx Systems and Leyden Labs. GA has served as a scientific advisor for Sanofi Vaccines. GA has collaborative agreements with GSK, Merck, Abbvie, Sanofi, Medicago, BioNtech, Moderna, BMS, Novavax, SK Biosciences, Gilead, and Sanaria. RAM has served as a scientific advisor for Valneva SE.

Research Funding:

Work in the Medina laboratory was partially funded by the FONDECYT 1212023 grant from ANID of Chile, the FLUOMICS Consortium (NIH-NIAID grant U19AI135972) and the Center for Research on Influenza Pathogenesis (CRIP), an NIAID Center of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C).

CPR and JL conducted this work as part of their Postdoctoral grant FONDECYT 3190706 and 3190648, respectively

MJA and ES conducted this work as part of their Ph.D. Thesis, under Programa de Doctorado en Ciencias Biológicas mención Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Cátolica de Chile.

MJA was funded by the ANID Becas/Doctorado Nacional 21212258 scholarship and ES was funded by a scholarship from Vicerrectoría de Investigación de la Escuela de Graduados, Pontificia Universidad Católica de Chile.

Keywords:

  • Vaccines
  • variants of concern
  • Omicron
  • antibodies
  • receptors
  • CoronaVac
  • Spike
  • Receptor-binding domain

Waning and boosting of functional humoral immunity to SARS-CoV-2

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bioRxiv

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Type of Work:

Article | Preprint: Prior to Peer Review

Abstract:

Since the emergence of the SARS-CoV-2 virus, we have witnessed a revolution in vaccine development with the rapid emergence and deployment of both traditional and novel vaccine platforms. The inactivated CoronaVac vaccine and the mRNA-based Pfizer/BNT162b2 vaccine are among the most widely distributed vaccines, both demonstrating high, albeit variable, vaccine effectiveness against severe COVID-19 over time. Beyond the ability of the vaccines to generate neutralizing antibodies, antibodies can attenuate disease via their ability to recruit the cytotoxic and opsinophagocytic functions of the immune response. However, whether Fc-effector functions are induced differentially, wane with different kinetics, and are boostable, remains unknown. Here, using systems serology, we profiled the Fc-effector profiles induced by the CoronaVac and BNT162b2 vaccines, over time. Despite the significantly higher antibody functional responses induced by the BNT162b2 vaccine, CoronaVac responses waned more slowly, albeit still found at levels below those present in the systemic circulation of BNT162b2 immunized individuals. However, mRNA boosting of the CoronaVac vaccine responses resulted in the induction of significantly higher peak antibody functional responses with increased humoral breadth, including to Omicron. Collectively, the data presented here point to striking differences in vaccine platform-induced functional humoral immune responses, that wane with different kinetics, and can be functionally rescued and expanded with boosting.

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This is an Open Access work distributed under the terms of the Creative Commons Attribution-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nd/4.0/rdf).
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