Hybrid immunity expands the functional humoral footprint of both mRNA and vector-based SARS-CoV-2 vaccines

Paulina Kaplonek; Yixiang Deng; Jessica Shih-Lu Lee; Heather J Zar; Dace Zavadska; Marina Johnson; Douglas A Lauffenburger; David Goldblatt; Galit Alter

doi:10.1016/j.xcrm.2023.101048

Hybrid immunity expands the functional humoral footprint of both mRNA and vector-based SARS-CoV-2 vaccines

Paulina Kaplonek, Yixiang Deng, Jessica Shih-Lu Lee, Heather J Zar, Dace Zavadska, Marina Johnson, Douglas A Lauffenburger, David Goldblatt (Corresponding Author), Galit Alter (Corresponding Author)

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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.

Original language	English
Article number	101048
Journal	Cell Reports Medicine
Volume	4
Issue number	5
DOIs	https://doi.org/10.1016/j.xcrm.2023.101048
Publication status	Published - 16 May 2023
Externally published	Yes

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

Field of Science*

3.2 Clinical medicine

Publication Type*

1.1. Scientific article indexed in Web of Science and/or Scopus database

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.xcrm.2023.101048Licence: CC BY-NC-ND

Hybrid immunity expandsFinal published version, 4.14 MBLicence: CC BY-NC-ND

Cite this

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title = "Hybrid immunity expands the functional humoral footprint of both mRNA and vector-based SARS-CoV-2 vaccines",

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.",

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",

author = "Paulina Kaplonek and Yixiang Deng and {Shih-Lu Lee}, Jessica and Zar, {Heather J} and Dace Zavadska and Marina Johnson and Lauffenburger, {Douglas A} and David Goldblatt and Galit Alter",

note = "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: {\textcopyright} 2023",

year = "2023",

month = may,

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doi = "10.1016/j.xcrm.2023.101048",

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AU - Zar, Heather J

AU - Zavadska, Dace

AU - Johnson, Marina

AU - Lauffenburger, Douglas A

AU - Goldblatt, David

AU - Alter, Galit

N1 - 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

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N2 - 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.

AB - 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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KW - SARS-CoV-2/genetics

KW - Breakthrough Infections

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VL - 4

JO - Cell Reports Medicine

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M1 - 101048

ER -

Hybrid immunity expands the functional humoral footprint of both mRNA and vector-based SARS-CoV-2 vaccines

Abstract

Keywords*

Field of Science*

Publication Type*

UN SDGs

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