Cell
Volume 185, Issue 6, 17 March 2022, Pages 1025-1040.e14
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Article
Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination

https://doi.org/10.1016/j.cell.2022.01.018Get rights and content
Under a Creative Commons license
open access

Highlights

  • Vaccination confers broader IgG binding of variant RBDs than SARS-CoV-2 infection

  • Imprinting from initial antigen exposures alters IgG responses to viral variants

  • Histology of mRNA vaccinee lymph nodes shows abundant GCs

  • Vaccine spike antigen and mRNA persist for weeks in lymph node GCs

Summary

During the SARS-CoV-2 pandemic, novel and traditional vaccine strategies have been deployed globally. We investigated whether antibodies stimulated by mRNA vaccination (BNT162b2), including third-dose boosting, differ from those generated by infection or adenoviral (ChAdOx1-S and Gam-COVID-Vac) or inactivated viral (BBIBP-CorV) vaccines. We analyzed human lymph nodes after infection or mRNA vaccination for correlates of serological differences. Antibody breadth against viral variants is lower after infection compared with all vaccines evaluated but improves over several months. Viral variant infection elicits variant-specific antibodies, but prior mRNA vaccination imprints serological responses toward Wuhan-Hu-1 rather than variant antigens. In contrast to disrupted germinal centers (GCs) in lymph nodes during infection, mRNA vaccination stimulates robust GCs containing vaccine mRNA and spike antigen up to 8 weeks postvaccination in some cases. SARS-CoV-2 antibody specificity, breadth, and maturation are affected by imprinting from exposure history and distinct histological and antigenic contexts in infection compared with vaccination.

Keywords

COVID-19
BioNTech-Pfizer
BNT162b2
Moderna
mRNA-1273
Astra Zeneca
ChAdOx1-S
Sputnik V
Gam-COVID-Vac
Sinopharm
BBIBP-CorV
vaccine
SARS-CoV-2
imprinting
SARS-CoV-2 variants of concern
Delta variant
endemic coronaviruses
antibodies
lymph node germinal center
autopsy

Data and code availability

Raw data from all serology Figures have been deposited on Mendeley at https://doi.org/10.17632/j8r94pfrj6.1 and are publicly available as of the date of publication. All original code has been deposited on the Zenodo platform at https://doi.org/10.5281/zenodo.5854880 and is publicly available at the Github repository https://github.com/boyd-lab/covid-infection-vs-vaccination as of the date of publication. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

14

These authors contributed equally

15

These authors contributed equally

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Lead contact