Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals

Katlyn Lederer; Emily Bettini; Kalpana Parvathaneni; Mark M Painter; Divyansh Agarwal; Kendall A Lundgreen; Madison Weirick; Kavitha Muralidharan; Diana Castaño; Rishi R Goel; Xiaoming Xu; Elizabeth M Drapeau; Sigrid Gouma; Jordan T Ort; Moses Awofolaju; Allison R Greenplate; Carole Le Coz; Neil Romberg; Jennifer Trofe-Clark; Gregory Malat; Lisa Jones; Mark Rosen; Daniela Weiskopf; Alessandro Sette; Behdad Besharatian; Mary Kaminiski; Scott E Hensley; Paul Bates; E John Wherry; Ali Naji; Vijay Bhoj; Michela Locci

doi:10.1016/j.cell.2022.01.027

Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals

Cell. 2022 Mar 17;185(6):1008-1024.e15. doi: 10.1016/j.cell.2022.01.027. Epub 2022 Feb 2.

Authors

Katlyn Lederer¹, Emily Bettini¹, Kalpana Parvathaneni², Mark M Painter³, Divyansh Agarwal⁴, Kendall A Lundgreen⁵, Madison Weirick¹, Kavitha Muralidharan², Diana Castaño⁶, Rishi R Goel³, Xiaoming Xu⁷, Elizabeth M Drapeau¹, Sigrid Gouma¹, Jordan T Ort¹, Moses Awofolaju¹, Allison R Greenplate³, Carole Le Coz⁸, Neil Romberg⁸, Jennifer Trofe-Clark⁹, Gregory Malat⁹, Lisa Jones¹⁰, Mark Rosen¹⁰, Daniela Weiskopf¹¹, Alessandro Sette¹², Behdad Besharatian¹³, Mary Kaminiski¹⁴, Scott E Hensley¹, Paul Bates⁵, E John Wherry³, Ali Naji¹⁵, Vijay Bhoj¹⁶, Michela Locci¹⁷

Affiliations

¹ Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
² Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
³ Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA.
⁴ Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
⁵ Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁶ Grupo de Inmunología Celular e Inmunogenética, Facultad de Medicina, Universidad de Antioquia, Medellín, Antioquia 050010, Colombia.
⁷ Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁸ Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Immunology and Allergy, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
⁹ Department of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
¹⁰ Department of Radiology, Division of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
¹¹ Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, La Jolla, CA 92037, USA.
¹² Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, La Jolla, CA 92037, USA; Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, La Jolla, CA 92093, USA.
¹³ Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
¹⁴ Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
¹⁵ Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: [email protected].
¹⁶ Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, PA 19104, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: [email protected].
¹⁷ Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: [email protected].

Abstract

Vaccine-mediated immunity often relies on the generation of protective antibodies and memory B cells, which commonly stem from germinal center (GC) reactions. An in-depth comparison of the GC responses elicited by SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals has not yet been performed due to the challenge of directly probing human lymph nodes. Herein, through a fine-needle aspiration-based approach, we profiled the immune responses to SARS-CoV-2 mRNA vaccines in lymph nodes of healthy individuals and kidney transplant recipients (KTXs). We found that, unlike healthy subjects, KTXs presented deeply blunted SARS-CoV-2-specific GC B cell responses coupled with severely hindered T follicular helper cell, SARS-CoV-2 receptor binding domain-specific memory B cell, and neutralizing antibody responses. KTXs also displayed reduced SARS-CoV-2-specific CD4 and CD8 T cell frequencies. Broadly, these data indicate impaired GC-derived immunity in immunocompromised individuals and suggest a GC origin for certain humoral and memory B cell responses following mRNA vaccination.

Keywords: SARS-CoV-2; T follicular helper cells; fine-needle aspiration; germinal center B cells; germinal centers; immunocompromised; kidney transplant recipients; mRNA vaccines; memory B cells; neutralizing antibodies.

Abstract

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