Imprinted SARS-CoV-2-specific memory lymphocytes define hybrid immunity

Rodda, Lauren B.; Morawski, Peter A.; Pruner, Kurt B.; Fahning, Mitchell L.; Howard, Christian A.; Franko, Nicholas; Logue, Jennifer; Eggenberger, Julie; Stokes, Caleb; Golez, Inah; Hale, Malika; Gale, Michael; Chu, Helen Y.; Campbell, Daniel; Pepper, Marion

doi:10.1016/j.cell.2022.03.018

Cited by 171 publications

(160 citation statements)

References 75 publications

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“…The hierarchy of the magnitude of the memory CD4 + T cells was mRNA-1273>BNT162b2~NVX-CoV2373>Ad26.COV2.S. These overall findings are consistent with previous reports on COVID-19 vaccine T cell responses (Barouch et al, 2021;Goel et al, 2021;Guerrera et al, 2021;Khoo et al, 2022;Liu et al, 2022;Mateus et al, 2021;Rodda et al, 2022;Tarke et al, 2022), but the analysis reported herein extensively expand these observations, including four different vaccines representing three different vaccine platforms, and with longitudinal data and single-cell cytokine expression resolution providing insights regarding CD4 + T cell subpopulations between the vaccines. Interestingly, multifunctional CD4 + T cells were observed most frequently after mRNA-1273 immunization, and CD4-CTLs represented a substantial fraction of the memory CD4 + T cells after mRNA-1273, BNT162b2, or NVX-CoV2373 vaccination.…”

Section: Discussionsupporting

confidence: 90%

Humoral and cellular immune memory to four COVID-19 vaccines

Zhang

Mateus

Coelho

et al. 2022

Preprint

119

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Multiple COVID-19 vaccines, representing diverse vaccine platforms, successfully protect against symptomatic COVID-19 cases and deaths. Head-to-head comparisons of T cell, B cell, and antibody responses to diverse vaccines in humans are likely to be informative for understanding protective immunity against COVID-19, with particular interest in immune memory. Here, SARS-CoV-2-spike-specific immune responses to Moderna mRNA-1273, Pfizer/BioNTech BNT162b2, Janssen Ad26.COV2.S and Novavax NVX-CoV2373 were examined longitudinally for 6 months. 100% of individuals made memory CD4+ T cells, with cTfh and CD4-CTL highly represented after mRNA or NVX-CoV2373 vaccination. mRNA vaccines and Ad26.COV2.S induced comparable CD8+ T cell frequencies, though memory CD8+ T cells were only detectable in 60-67% of subjects at 6 months. Ad26.COV2.S was not the strongest immunogen by any measurement, though the Ad26.COV2.S T cell, B cell, and antibody responses were relatively stable over 6 months. A differentiating feature of Ad26.COV2.S immunization was a high frequency of CXCR3+ memory B cells. mRNA vaccinees had substantial declines in neutralizing antibodies, while memory T cells and B cells were comparatively stable over 6 months. These results of these detailed immunological evaluations may also be relevant for vaccine design insights against other pathogens.

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Section: Discussionsupporting

confidence: 90%

Humoral and cellular immune memory to four COVID-19 vaccines

Zhang

Mateus

Coelho

et al. 2022

Preprint

119

View full text Add to dashboard Cite

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“…determined that previously infected individuals generated more SARS-CoV-2-specific memory B cells, neutralizing antibodies, and a distinctive population of S-specific CD4 T cells expressing IFNγ and IL10 after vaccination than naïve-vaccinated individuals ( Rodda et al., 2022 ). Interestingly, additional vaccinations did not elicit these same CD4 T cell profiles, suggesting that immune imprinting may underlie the unique immune signatures associated with hybrid immunity to SARS-CoV-2 ( Rodda et al., 2022 ).…”

Section: Adaptive Respiratory Immune Response: B Lymphocytesmentioning

confidence: 99%

Mucosal immune responses to infection and vaccination in the respiratory tract

Mettelman

Allen²,

Thomas³

2022

Immunity

123

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“…The ability to modify the functional profile of classical Th1 T cells can be of particular importance in SARS-CoV-2 infection. The presence and induction of both IL-10– and IFN-γ–producing SARS-CoV-2–specific T cells are associated with asymptomatic SARS-CoV-2 infection ( 28 ) and hybrid immunity ( 29 ), while their absence has been reported in severe COVID-19 ( 30 ). The induction of such T cells endowed with antiinflammatory potential might be advantageous in the asymptomatic control of SARS-CoV-2 infection.…”

Section: Introductionmentioning

confidence: 99%

Favorable vaccine-induced SARS-CoV-2–specific T cell response profile in patients undergoing immune-modifying therapies

Qui¹,

Bert²,

Chan³

et al. 2022

Journal of Clinical Investigation

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BACKGROUND Patients undergoing immune-modifying therapies demonstrate a reduced humoral response after COVID-19 vaccination, but we lack a proper evaluation of the effect of such therapies on vaccine-induced T cell responses. METHODS We longitudinally characterized humoral and spike-specific T cell responses in patients with inflammatory bowel disease (IBD), who were on antimetabolite therapy (azathioprine or methotrexate), TNF inhibitors, and/or other biologic treatment (anti-integrin or anti-p40) for up to 6 months after completing 2-dose COVID-19 mRNA vaccination. RESULTS We demonstrate that a spike-specific T cell response was not only induced in treated patients with IBD at levels similar to those of healthy individuals, but also sustained at higher magnitude for up to 6 months after vaccination, particularly in those treated with TNF inhibitor therapy. Furthermore, the spike-specific T cell response in these patients was mainly preserved against mutations present in SARS-CoV-2 B.1.1.529 (Omicron) and characterized by a Th1/IL-10 cytokine profile. CONCLUSION Despite the humoral response defects, patients under immune-modifying therapies demonstrated a favorable profile of vaccine-induced T cell responses that might still provide a layer of COVID-19 protection. FUNDING This study was funded by the National Centre for Infectious Diseases (NCID) Catalyst Grant (FY2021ES) and the National Research Fund Competitive Research Programme (NRF-CRP25-2020-0003).

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Imprinted SARS-CoV-2-specific memory lymphocytes define hybrid immunity

Cited by 171 publications

References 75 publications

Humoral and cellular immune memory to four COVID-19 vaccines

Humoral and cellular immune memory to four COVID-19 vaccines

Mucosal immune responses to infection and vaccination in the respiratory tract

Favorable vaccine-induced SARS-CoV-2–specific T cell response profile in patients undergoing immune-modifying therapies

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