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 (Coresponding Author), Galit Alter (Coresponding Author)

Research output: Contribution to journalArticlepeer-review

1 Downloads (Pure)


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 languageEnglish
Article number101048
JournalCell Reports Medicine
Issue number5
Publication statusPublished - 16 May 2023
Externally publishedYes


  • 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


Dive into the research topics of 'Hybrid immunity expands the functional humoral footprint of both mRNA and vector-based SARS-CoV-2 vaccines'. Together they form a unique fingerprint.

Cite this