Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection

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Abstract

Understanding immune memory to SARS-CoV-2 is critical for improving diagnostics and vaccines, and for assessing the likely future course of the COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at ≥ 6 months post-infection. IgG to the Spike protein was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month post symptom onset. SARS-CoV-2-specific CD4 ⁺ T cells and CD8 ⁺ T cells declined with a half-life of 3-5 months. By studying antibody, memory B cell, CD4 ⁺ T cell, and CD8 ⁺ T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.

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Most cited references 24

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T Follicular Helper Cell Biology: A Decade of Discovery and Diseases

Shane Crotty (2019)

Helping B cells and antibody responses is a major function of CD4+ T cells. It has been 10 years since the publication of Bcl6 as the lineage-defining transcription factor for T follicular helper (Tfh) differentiation and the requirement of Tfh cells as the specialized subset of CD4+ T cells needed for germinal centers (the microanatomical sites of B cell mutation and antibody affinity maturation) and related B cell responses. A great deal has been learned about Tfh cells in the past 10 years, particularly regarding their roles in a surprising range of diseases. Advances in the understanding of Tfh cell differentiation and function are discussed, as are the understanding of Tfh cells in infectious diseases, vaccines, autoimmune diseases, allergies, atherosclerosis, organ transplants, and cancer. This includes discussion of Tfh cells in the human immune system. Based on the discoveries to date, the next decade of Tfh research surely holds many more surprises. VIDEO ABSTRACT.

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Vaccines: correlates of vaccine-induced immunity.

Stanley Plotkin (2008)

The immune system is redundant, and B and T cells collaborate. However, almost all current vaccines work through induction of antibodies in serum or on mucosa that block infection or interfere with microbial invasion of the bloodstream. To protect, antibodies must be functional in the sense of neutralization or opsonophagocytosis. Correlates of protection after vaccination are sometimes absolute quantities but often are relative, such that most infections are prevented at a particular level of response but some will occur above that level because of a large challenge dose or deficient host factors. There may be >1 correlate of protection for a disease, which we term "cocorrelates." Either effector or central memory may correlate with protection. Cell-mediated immunity also may operate as a correlate or cocorrelate of protection against disease, rather than against infection. In situations where the true correlate of protection is unknown or difficult to measure, surrogate tests (usually antibody measurements) must suffice as predictors of protection by vaccines. Examples of each circumstance are given.

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Duration of antiviral immunity after smallpox vaccination.

Erika Hammarlund, Matthew W Lewis, Scott G Hansen … (2003)

Although naturally occurring smallpox was eliminated through the efforts of the World Health Organization Global Eradication Program, it remains possible that smallpox could be intentionally released. Here we examine the magnitude and duration of antiviral immunity induced by one or more smallpox vaccinations. We found that more than 90% of volunteers vaccinated 25-75 years ago still maintain substantial humoral or cellular immunity (or both) against vaccinia, the virus used to vaccinate against smallpox. Antiviral antibody responses remained stable between 1-75 years after vaccination, whereas antiviral T-cell responses declined slowly, with a half-life of 8-15 years. If these levels of immunity are considered to be at least partially protective, then the morbidity and mortality associated with an intentional smallpox outbreak would be substantially reduced because of pre-existing immunity in a large number of previously vaccinated individuals.

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Author and article information

Journal

Journal ID (nlm-ta): Science

Journal ID (iso-abbrev): Science

Journal ID (publisher-id): SCIENCE

Title: Science (New York, N.y.)

Publisher: American Association for the Advancement of Science

ISSN (Print): 0036-8075

ISSN (Electronic): 1095-9203

Publication date (Electronic): 06 January 2021

Electronic Location Identifier: eabf4063

Affiliations

[1 ]Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.

[2 ]Department of Medicine, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.

[3 ]Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA 92037, USA.

[4 ]Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

[5 ]Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

[6 ]The Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Author notes

[*]

These authors contributed equally to this work.

[† ]Corresponding author. Email: shane@ 123456lji.org (S.C.); alex@ 123456lji.org (A.S.); daniela@ 123456lji.org (D.W.)

Author information

Jennifer M. Dan https://orcid.org/0000-0002-1672-0657

Jose Mateus https://orcid.org/0000-0002-1402-3452

Yu Kato https://orcid.org/0000-0003-4743-1775

Kathryn M. Hastie https://orcid.org/0000-0002-3406-1210

Esther Dawen Yu https://orcid.org/0000-0002-3970-3753

Alba Grifoni https://orcid.org/0000-0002-2209-5966

Sydney I. Ramirez https://orcid.org/0000-0002-7166-5195

Sonya Haupt https://orcid.org/0000-0002-8371-3713

April Frazier https://orcid.org/0000-0002-4722-7304

Vamseedhar Rayaprolu https://orcid.org/0000-0002-2823-2984

Stephen A. Rawlings https://orcid.org/0000-0003-3637-1447

Bjoern Peters https://orcid.org/0000-0002-8457-6693

Florian Krammer https://orcid.org/0000-0003-4121-776X

Viviana Simon https://orcid.org/0000-0002-6416-5096

Erica Ollmann Saphire https://orcid.org/0000-0002-1206-7451

Davey M. Smith https://orcid.org/0000-0003-3603-1733

Daniela Weiskopf https://orcid.org/0000-0003-2968-7371

Alessandro Sette https://orcid.org/0000-0001-7013-2250

Shane Crotty https://orcid.org/0000-0002-6484-6262

Article

Publisher ID: abf4063

DOI: 10.1126/science.abf4063

PMC ID: 7919858

PubMed ID: 33408181

SO-VID: 691f323e-cd2e-4b56-b55f-223b5b5c252f

Copyright © Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

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This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 23 October 2020

Date accepted : 23 December 2020

Funding

Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;

Award ID: Nr. 75N9301900065

Funded by: doi http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;

Award ID: AI142742

Funded by: doi http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;

Award ID: AI135078

Funded by: doi http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;

Award ID: HHSN272201400008C

Funded by: doi http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;

Award ID: 75N93019C00051

Funded by: doi http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;

Award ID: AI007036

Funded by: doi http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;

Award ID: U01 AI141995

Funded by: doi http://dx.doi.org/10.13039/100000865, Bill and Melinda Gates Foundation;

Award ID: INV-006133

Funded by: doi http://dx.doi.org/10.13039/100010269, Wellcome;

Award ID: INV-006133

Funded by: Mastercard Incorporated;

Award ID: INV-006133

Funded by: doi http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;

Award ID: AI141995-03

Funded by: doi http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;

Award ID: U01 CA260541-01

Funded by: doi http://dx.doi.org/10.13039/100007457, JPB Foundation;

Funded by: doi http://dx.doi.org/10.13039/100014895, Open Philanthropy Project;

Award ID: 2020-215611

Funded by: doi http://dx.doi.org/10.13039/100016230, Steven and Alexandra Cohen Foundation;

Funded by: John and Mary Tu Foundation;

Funded by: doi http://dx.doi.org/10.13039/100000060, National Institute of Allergy and Infectious Diseases;

Award ID: AI007384

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Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection

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Novel Coronavirus Disease COVID-19

Most cited references 24

T Follicular Helper Cell Biology: A Decade of Discovery and Diseases

Vaccines: correlates of vaccine-induced immunity.

Duration of antiviral immunity after smallpox vaccination.

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