Hybrid immunity expands the functional humoral footprint of both mRNA and vector-based SARS-CoV-2 vaccines
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Date
2023-05-16
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Abstract
Despite the successes of current coronavirus disease 2019 (COVID-19) vaccines, waning immunity, the emergence of variants of concern, and breakthrough infections among vaccinees have begun to highlight opportunities to improve vaccine platforms. Real-world vaccine efficacy studies have highlighted the reduced risk of breakthrough infections and diseases among individuals infected and vaccinated, referred to as hybrid immunity. Thus, we sought to define whether hybrid immunity shapes the humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) following Pfizer/BNT162b2, Moderna mRNA-1273, ChadOx1/AZD1222, and Ad26.COV2.S vaccination. Each vaccine exhibits a unique functional humoral profile in vaccination only or hybrid immunity. However, hybrid immunity shows a unique augmentation of S2-domain-specific functional immunity that was poorly induced for the vaccination only. These data highlight the importance of natural infection in breaking the immunodominance away from the evolutionarily unstable S1 domain and potentially affording enhanced cross-variant protection by targeting the more highly conserved S2 domain of SARS-CoV-2.
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Funding Information: We thank Nancy Zimmerman, Mark and Lisa Schwartz, an anonymous donor (financial support), Terry and Susan Ragon, and the SAMANA Kay MGH Research Scholars award for support. We acknowledge support from the Ragon Institute of Mass General, MIT, and Harvard (to G.A.) the Massachusetts Consortium on Pathogen Readiness (MassCPR) (to G.A.), and the National Institutes of Health ( 3R37AI080289-11S1 , R01AI146785 , U19AI42790–01 , U19AI135995–02 , U19AI42790-01 , 1U01CA260476 – 01 , and CIVIC75N93019C00052 ) (to G.A.). Publisher Copyright: © 2023
Keywords
Humans, COVID-19 Vaccines, RNA, Messenger/genetics, Ad26COVS1, BNT162 Vaccine, ChAdOx1 nCoV-19, COVID-19/prevention & control, SARS-CoV-2/genetics, Breakthrough Infections, Immunity, Humoral, 3.2 Clinical medicine, 1.1. Scientific article indexed in Web of Science and/or Scopus database, SDG 3 - Good Health and Well-being
Citation
Kaplonek, P, Deng, Y, Shih-Lu Lee, J, Zar, H J, Zavadska, D, Johnson, M, Lauffenburger, D A, Goldblatt, D & Alter, G 2023, 'Hybrid immunity expands the functional humoral footprint of both mRNA and vector-based SARS-CoV-2 vaccines', Cell Reports Medicine, vol. 4, no. 5, 101048. https://doi.org/10.1016/j.xcrm.2023.101048