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

Cell Rep Med. 2023 May 16;4(5):101048. doi: 10.1016/j.xcrm.2023.101048. Epub 2023 Apr 25.

Authors

Paulina Kaplonek¹, Yixiang Deng², Jessica Shih-Lu Lee¹, Heather J Zar³, Dace Zavadska⁴, Marina Johnson⁵, Douglas A Lauffenburger⁶, David Goldblatt⁷, Galit Alter⁸

Affiliations

¹ Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA, USA.
² Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
³ Department of Pediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa; SA MRC Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa.
⁴ Children's Clinical University Hospital, Riga, Latvia.
⁵ Great Ormond Street Institute of Child Health Biomedical Research Centre, University College London, London, UK.
⁶ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁷ Great Ormond Street Institute of Child Health Biomedical Research Centre, University College London, London, UK. Electronic address: d.goldblatt@ucl.ac.uk.
⁸ Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA, USA. Electronic address: galter@mgh.harvard.edu.

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: COVID-19; FcR binding; SARS-CoV-2; VOCs; antibody; antibody functions; mRNA vaccine; vaccine; vector vaccine.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Ad26COVS1
BNT162 Vaccine
Breakthrough Infections
COVID-19 Vaccines*
COVID-19* / prevention & control
ChAdOx1 nCoV-19
Humans
Immunity, Humoral
RNA, Messenger / genetics
SARS-CoV-2 / genetics

Substances

COVID-19 Vaccines
RNA, Messenger
Ad26COVS1
BNT162 Vaccine
ChAdOx1 nCoV-19

Abstract

Publication types

MeSH terms

Substances

Grants and funding