Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination

Katharina Röltgen; Sandra C A Nielsen; Oscar Silva; Sheren F Younes; Maxim Zaslavsky; Cristina Costales; Fan Yang; Oliver F Wirz; Daniel Solis; Ramona A Hoh; Aihui Wang; Prabhu S Arunachalam; Deana Colburg; Shuchun Zhao; Emily Haraguchi; Alexandra S Lee; Mihir M Shah; Monali Manohar; Iris Chang; Fei Gao; Vamsee Mallajosyula; Chunfeng Li; James Liu; Massa J Shoura; Sayantani B Sindher; Ella Parsons; Naranjargal J Dashdorj; Naranbaatar D Dashdorj; Robert Monroe; Geidy E Serrano; Thomas G Beach; R Sharon Chinthrajah; Gregory W Charville; James L Wilbur; Jacob N Wohlstadter; Mark M Davis; Bali Pulendran; Megan L Troxell; George B Sigal; Yasodha Natkunam; Benjamin A Pinsky; Kari C Nadeau; Scott D Boyd

doi:10.1016/j.cell.2022.01.018

Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination

Cell. 2022 Mar 17;185(6):1025-1040.e14. doi: 10.1016/j.cell.2022.01.018. Epub 2022 Jan 25.

Authors

Katharina Röltgen¹, Sandra C A Nielsen¹, Oscar Silva¹, Sheren F Younes¹, Maxim Zaslavsky¹, Cristina Costales¹, Fan Yang¹, Oliver F Wirz¹, Daniel Solis¹, Ramona A Hoh¹, Aihui Wang¹, Prabhu S Arunachalam², Deana Colburg¹, Shuchun Zhao¹, Emily Haraguchi¹, Alexandra S Lee³, Mihir M Shah³, Monali Manohar³, Iris Chang³, Fei Gao², Vamsee Mallajosyula², Chunfeng Li², James Liu⁴, Massa J Shoura¹, Sayantani B Sindher³, Ella Parsons³, Naranjargal J Dashdorj⁵, Naranbaatar D Dashdorj⁶, Robert Monroe⁷, Geidy E Serrano⁸, Thomas G Beach⁸, R Sharon Chinthrajah⁹, Gregory W Charville¹, James L Wilbur¹⁰, Jacob N Wohlstadter¹⁰, Mark M Davis¹¹, Bali Pulendran¹², Megan L Troxell¹, George B Sigal¹⁰, Yasodha Natkunam¹, Benjamin A Pinsky¹³, Kari C Nadeau⁹, Scott D Boyd¹⁴

Affiliations

¹ Department of Pathology, Stanford University, Stanford, CA, USA.
² Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
³ Sean N. Parker Center for Allergy & Asthma Research, Stanford University, Stanford, CA, USA.
⁴ Stanford Health Library, Stanford, CA, USA.
⁵ Onom Foundation, Ulaanbaatar 17013, Mongolia; Liver Center, Ulaanbaatar 14230, Mongolia.
⁶ Onom Foundation, Ulaanbaatar 17013, Mongolia.
⁷ Advanced Cell Diagnostics, Newark, CA, USA.
⁸ Banner Sun Health Research Institute, Sun City, AZ, USA.
⁹ Sean N. Parker Center for Allergy & Asthma Research, Stanford University, Stanford, CA, USA; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Stanford University, Stanford, CA, USA.
¹⁰ Meso Scale Diagnostics LLC, Rockville, MD, USA.
¹¹ Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA.
¹² Department of Pathology, Stanford University, Stanford, CA, USA; Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
¹³ Department of Pathology, Stanford University, Stanford, CA, USA; Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, USA.
¹⁴ Department of Pathology, Stanford University, Stanford, CA, USA; Sean N. Parker Center for Allergy & Asthma Research, Stanford University, Stanford, CA, USA. Electronic address: publications_scott_boyd@stanford.edu.

Abstract

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

Publication types

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

MeSH terms

Antibodies, Viral*
Antigens, Viral
BNT162 Vaccine*
COVID-19* / prevention & control
Germinal Center*
Humans
SARS-CoV-2 / genetics
Spike Glycoprotein, Coronavirus
Vaccination

Substances

Antibodies, Viral
Antigens, Viral
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
BNT162 Vaccine

Supplementary concepts

SARS-CoV-2 variants

Abstract

Publication types

MeSH terms

Substances

Supplementary concepts

Grants and funding