mRNA COVID-19 vaccine elicits potent adaptive immune response without the acute inflammation of SARS-CoV-2 infection
Ellie N. Ivanova,
Jasmine Shwetar,
Joseph C. Devlin,
Terkild B. Buus,
Sophie Gray-Gaillard,
Akiko Koide,
Amber Cornelius,
Marie I. Samanovic,
Alberto Herrera,
Eleni P. Mimitou,
Chenzhen Zhang,
Trishala Karmacharya,
Ludovic Desvignes,
Niels Ødum,
Peter Smibert,
Robert J. Ulrich,
Mark J. Mulligan,
Shohei Koide,
Kelly V. Ruggles,
Ramin S. Herati,
Sergei B. Koralov
Affiliations
Ellie N. Ivanova
Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA
Jasmine Shwetar
Institute of Systems Genetics, New York University Grossman School of Medicine, New York, NY 10016, USA; Vilcek Institute of Graduate Biomedical Sciences, New York University Grossman School of Medicine, New York, NY 10016, USA
Joseph C. Devlin
Institute of Systems Genetics, New York University Grossman School of Medicine, New York, NY 10016, USA; Vilcek Institute of Graduate Biomedical Sciences, New York University Grossman School of Medicine, New York, NY 10016, USA
Terkild B. Buus
Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA; LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Sophie Gray-Gaillard
New York University Langone Vaccine Center, New York University Langone Health, New York, NY 10016, USA
Akiko Koide
Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA; Perlmutter Cancer Center, New York University Langone Health, New York, NY 10016, USA
Amber Cornelius
New York University Langone Vaccine Center, New York University Langone Health, New York, NY 10016, USA
Marie I. Samanovic
New York University Langone Vaccine Center, New York University Langone Health, New York, NY 10016, USA; Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA
Alberto Herrera
Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA
Eleni P. Mimitou
New York Genome Center, New York, NY 10013, USA
Chenzhen Zhang
Vilcek Institute of Graduate Biomedical Sciences, New York University Grossman School of Medicine, New York, NY 10016, USA
Trishala Karmacharya
New York University Langone Vaccine Center, New York University Langone Health, New York, NY 10016, USA
Ludovic Desvignes
New York University Langone Vaccine Center, New York University Langone Health, New York, NY 10016, USA; Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA; High Containment Laboratories, Office of Science and Research, New York University Langone Health, New York, NY 10016, USA
Niels Ødum
LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, 2200 Copenhagen, Denmark
Peter Smibert
New York Genome Center, New York, NY 10013, USA
Robert J. Ulrich
New York University Langone Vaccine Center, New York University Langone Health, New York, NY 10016, USA; Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA
Mark J. Mulligan
New York University Langone Vaccine Center, New York University Langone Health, New York, NY 10016, USA
Shohei Koide
Perlmutter Cancer Center, New York University Langone Health, New York, NY 10016, USA; Department of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY 10016, USA
Kelly V. Ruggles
Institute of Systems Genetics, New York University Grossman School of Medicine, New York, NY 10016, USA; Corresponding author
Ramin S. Herati
New York University Langone Vaccine Center, New York University Langone Health, New York, NY 10016, USA; Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016, USA; Department of Microbiology, New York University Grossman School of Medicine, 430 East 29th Street, New York, NY 10016, USA; Corresponding author
Sergei B. Koralov
Department of Pathology, New York University Grossman School of Medicine, New York, NY 10016, USA; Corresponding author
Summary: SARS-CoV-2 infection and vaccination elicit potent immune responses. Our study presents a comprehensive multimodal single-cell analysis of blood from COVID-19 patients and healthy volunteers receiving the SARS-CoV-2 vaccine and booster. We profiled immune responses via transcriptional analysis and lymphocyte repertoire reconstruction. COVID-19 patients displayed an enhanced interferon signature and cytotoxic gene upregulation, absent in vaccine recipients. B and T cell repertoire analysis revealed clonal expansion among effector cells in COVID-19 patients and memory cells in vaccine recipients. Furthermore, while clonal αβ T cell responses were observed in both COVID-19 patients and vaccine recipients, expansion of clonal γδ T cells was found only in infected individuals. Our dataset enables side-by-side comparison of immune responses to infection versus vaccination, including clonal B and T cell responses. Our comparative analysis shows that vaccination induces a robust, durable clonal B and T cell responses, without the severe inflammation associated with infection.