Cited by 499SARS-CoV-2 and COVID-19 ResearchT-cell and B-cell ImmunologyImmune responses and vaccinations

Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination

Open access
Painter, Mark M., Mathew, Divij, Goel, Rishi R., Apostolidis, Sokratis A., Pattekar, Ajinkya, Kuthuru, Oliva, Baxter, Amy E., Herati, Ramin S. +24 more·2021·Immunity

Abstract

SARS-CoV-2 mRNA vaccines have shown remarkable clinical efficacy, but questions remain about the nature and kinetics of T cell priming. We performed longitudinal antigen-specific T cell analyses on healthy SARS-CoV-2-naive and recovered individuals prior to and following mRNA prime and boost vaccination. Vaccination induced rapid antigen-specific CD4+ T cell responses in naive subjects after the first dose, whereas CD8+ T cell responses developed gradually and were variable in magnitude. Vaccine-induced Th1 and Tfh cell responses following the first dose correlated with post-boost CD8+ T cells and neutralizing antibodies, respectively. Integrated analysis revealed coordinated immune responses with distinct trajectories in SARS-CoV-2-naive and recovered individuals. Last, whereas booster vaccination improved T cell responses in SARS-CoV-2-naive subjects, the second dose had little effect in SARS-CoV-2-recovered individuals. These findings highlight the role of rapidly primed CD4+ T cells in coordinating responses to the second vaccine dose in SARS-CoV-2-naive individuals.

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Crossref · 10.1016/j.immuni.2021.08.001

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 30 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    In recovered individuals, the baseline AIM+ CD4+ T cell response consisted mostly of EM1 and CM cells.

    “The baseline AIM+ CD4+ T cell response in SARS-CoV-2-recovered individuals, presumably generated during prior SARS-CoV-2 infection, was composed mainly of EM1 (CD45RA− CD27+ CCR7−) and CM cells”
    Quote in the paperSubstantial claim
  • Findingown data

    People who had recovered from SARS-CoV-2 showed no significant rise in AIM+ CD8+ T cell frequency after either vaccine dose.

    “Individuals who had previously recovered from SARS-CoV-2 infection experienced no significant increase in the frequency of AIM+ CD8+ T cells from either dose of vaccine”
    Quote in the paperNot a substantial claim
  • Findingown data

    In these subjects, vaccine-primed AIM+ CD8+ T cells were mostly EM1, with smaller CM and EM3 populations.

    “vaccine-primed AIM+ CD8+ T cells in these subjects were largely EM1, with minority populations of CM and EM3 cells”
    Quote in the paperNot a substantial claim
  • Findingown data

    mRNA vaccination produced a CD4+ T cell response in everyone: all participants, whether previously infected or not, had higher AIM+ CD4+ T cell frequencies after the booster than before vaccination.

    “mRNA vaccination induced a universal CD4+ T cell response, as all individuals, regardless of prior infection with SARS-CoV-2, had greater frequencies of AIM+ CD4+ T cells post-boost than at pre-vaccine baseline”
    Quote in the paperSubstantial claim
  • Findingown data

    The size of AIM+ cTfh responses correlated with activated Ki67+CD38+ cTfh (CXCR5+PD-1+) measured in parallel after each dose.

    “The magnitude of AIM+ cTfh responses was correlated with activated (Ki67+CD38+) cTfh (CXCR5+PD-1+) analyzed in parallel after each vaccine dose”
    Quote in the paperNot a substantial claim
  • May combine two claims. 27
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 14
  • May combine two claims.

    Findingown data

    In recovered individuals, both UMAP1 and UMAP2 increased after the first dose but showed essentially no change after the second dose.

    “in SARS-CoV-2-recovered individuals, there was an increase in both UMAP1 and UMAP2 following primary vaccination but essentially no change following the second vaccine dose”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    A booster improves T cell responses in naive individuals, while a second dose has minimal effect in those previously infected.

    “whereas booster vaccination improved T cell responses in SARS-CoV-2-naive subjects, the second dose had little effect in SARS-CoV-2-recovered individuals.”
    • Also stated in: § Introduction · plain
      “the second dose further boosted both CD4+ and CD8+ T cell responses. In contrast, SARS-CoV-2-recovered individuals had maximal CD4+ and CD8+ T cell responses following the first dose of mRNA vaccine, and there was little additional T cell boosting after the second dose.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    In naive individuals, this distribution persisted through booster vaccination, and the second dose further increased these AIM+ subsets.

    “This distribution was sustained through booster vaccination in SARS-CoV-2-naive individuals, with these AIM+ subsets being further boosted by the second vaccine dose”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    Total non-naive lymphocyte populations did not change and did not correlate with antigen-specific responses.

    “Total non-naive lymphocyte populations were not altered and did not correlate with the antigen-specific responses”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    CD8+ T cell responses to mRNA vaccination develop gradually and vary in magnitude in SARS-CoV-2-naive individuals.

    “CD8+ T cell responses developed gradually and were variable in magnitude.”
    • Also stated in: § Prime-boost vaccination induces antigen-specific CD8+ T cells in most SARS-CoV-2-naive individuals · plain
      “SARS-CoV-2-specific CD8+ T cell responses developed more gradually and with greater variability in naive individuals.”
    • Also stated in: § Prime-boost vaccination induces antigen-specific CD8+ T cells in most SARS-CoV-2-naive individuals · plain
      “though the magnitude of response was variable”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Pre-boost Th1 cells correlated less with post-boost neutralizing titers than cTfh did, and pre-boost cTfh did not significantly correlate with post-boost CD8+ T cell responses.

    “pre-boost Th1 were less well correlated with post-boost neutralizing titers than were cTfh, and pre-boost cTfh did not significantly correlate with post-boost CD8+ T cell responses”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    Total non-naive CD8+ T cells were spread across memory subsets, and vaccination did not change the frequencies of those subsets.

    “Total non-naive CD8+ T cells were distributed throughout memory T cell subsets, and the frequencies of these subsets were unchanged by vaccination”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    A second dose boosted antigen-specific CD4+ T cells in naive individuals but not in those who had recovered from SARS-CoV-2.

    “SARS-CoV-2-naive individuals, but not recovered individuals, received an additional boost to antigen-specific CD4+ T cells following the second vaccine dose”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    In recovered subjects, these proportions remained fairly stable during vaccination, with no significant changes from baseline.

    “These proportions stayed relatively consistent throughout the course of vaccination in recovered subjects, and there were no statistically significant changes from baseline”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    The vaccine also increased antigen-specific CD4+ EM2 and EM3 cells, but these stayed less common than CM and EM1 cells.

    “Antigen-specific CD4+ EM2 (CD45RA− CD27− CCR7+) and EM3 (CD45RA− CD27− CCR7−) T cells, which share more effector-like properties (Romero et al., 2007), were also boosted by the vaccine but remained minority populations compared with CM and EM1”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    In naive subjects, baseline AIM+ Th1 and cTfh cells did not correlate with post-boost CD8+ T cell or neutralizing responses, respectively.

    “baseline AIM+ Th1 and cTfh cells in SARS-CoV-2-naive subjects did not correlate with post-boost CD8+ T cell or neutralizing responses, respectively”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    About 70% of recovered individuals appeared to have higher AIM+ CD8+ T cell frequencies than at baseline, but the group-level increase was not statistically significant.

    “A subset of recovered individuals (70%) did appear to have increased AIM+ CD8+ T cell frequencies compared with baseline, but as a group this increase did not reach statistical significance”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    The first mRNA vaccine dose strongly primed Spike-specific CD4+ T cells in both naive and recovered individuals, and every participant produced a detectable response.

    “SARS-CoV-2 Spike-specific CD4+ T cells were robustly primed in SARS-CoV-2-naive and recovered individuals following the first dose of mRNA vaccine, with all participants generating detectable responses to the first dose”
    Quote in the paperSubstantial claim
  • May combine two claims. The quote only partly states this claim.

    Findingown data

    An integrated analysis of 26 antigen-specific features shows that immune responses are coordinated and follow different trajectories in naive versus recovered individuals.

    “Integrated analysis revealed coordinated immune responses with distinct trajectories in SARS-CoV-2-naive and recovered individuals.”
    • Also stated in: § Integrated analysis reveals coordinated humoral and cellular responses to mRNA vaccination with distinct trajectories in SARS-CoV-2-naive and recovered individuals · plain
      “integrated 26 antigen-specific features of the immune response to mRNA vaccination into high-dimensional uniform manifold approximation and projection (UMAP) space”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    In recovered subjects, the first dose expanded AIM+ cTfh and Th1 cells further, and this pattern largely persisted throughout vaccination.

    “The first dose of vaccine led to further expansion of AIM+ cTfh and Th1 cells in these recovered subjects, and this pattern was largely maintained through the course of vaccination”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Interpretationown data

    Our data show that mRNA vaccination strongly induces antigen-specific T cells, which may add to previously described humoral responses in providing durable protection.

    “Our data demonstrate robust induction of antigen-specific T cells by mRNA vaccination that may contribute, in addition to previously defined humoral responses, to durable protective immunity.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Interpretationown data

    These findings point to an important functional role for vaccine-induced CD4+ T cells and suggest that skewed antigen-specific CD4+ T cell responses may have downstream effects.

    “These observations highlight a key functional role for vaccine-elicited CD4+ T cells and suggest possible downstream effects of skewed antigen-specific CD4+ T cell responses.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Whether CD4+ and CD8+ T cells are central memory or effector memory affects their persistence, circulation, tissue entry, and recall responses.

    “the central memory (CM) or effector memory (EM) differentiation states of CD4+ and CD8+ T cells have implications for durability, recirculation, tissue access, and responses upon antigen re-exposure (Kaech et al., 2002; Martin and Badovinac, 2018; Wherry et al., 2003).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Kaech et al., 2002 source

      Not checked in the free run.

    • cites Martin and Badovinac, 2018

      Not checked in the free run.

    • cites Wherry et al., 2003 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The AIM+ CD4+ T cell response to mRNA vaccination qualitatively resembled the response to natural infection and featured strong induction of antigen-specific cTfh and Th1 cells.

    “Thus, the vaccine-elicited AIM+ CD4+ T cell response to mRNA vaccination qualitatively resembled the response to natural infection and was characterized by robust induction of antigen-specific cTfh and Th1 cells.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Tfh cells are important for generating memory B cells, plasma cells, and antibodies, while Th1 cells help improve memory CD8+ T cell responses.

    “CD4+ T follicular helper (Tfh) cells have key roles in the development of memory B cells, plasma cells, and antibodies, whereas Th1 cells support and enhance the quality of memory CD8+ T cell responses (Crotty, 2011; Krawczyk et al., 2007; Luckheeram et al., 2012; Williams et al., 2006).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Crotty, 2011 source

      Not checked in the free run.

    • cites Krawczyk et al., 2007 source

      Not checked in the free run.

    • cites Luckheeram et al., 2012 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Each experiment used longitudinal samples from 36 naive and 11 recovered individuals, run in nine independent batches, with paired longitudinal samples always within one batch.

    “Longitudinal samples from 36 SARS-CoV-2-naive and 11 SARS-CoV-2-recovered individuals were used for each experiment, analyzed in nine independent batches. All paired longitudinal samples were analyzed within a single batch.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In blood cancer patients, CD8+ T cells may compensate for weak humoral immunity and have been linked to better outcomes, suggesting T cells help protect against SARS-CoV-2.

    “in patients with hematological malignancy, CD8+ T cells appear to compensate for lack of humoral immunity and were associated with improved outcomes, indicating a role for T cells in protection against SARS-CoV-2 infection (Bange et al., 2021).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Bange et al., 2021 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Strong T cell responses from mRNA vaccines may matter for long-term protection, since memory CD4+ and CD8+ T cells can last exceptionally long after other vaccines.

    “the generation of robust T cell responses by mRNA vaccines may have implications for long-term protective immunity, as memory CD4+ and CD8+ T cells can be exceptionally durable in other vaccine settings (Akondy et al., 2017; Hammarlund et al., 2003).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Akondy et al., 2017 source

      Not checked in the free run.

    • cites Hammarlund et al., 2003 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Some naive individuals had low pre-vaccination AIM+ T cell frequencies, possibly from cross-reactive cells generated by earlier seasonal coronavirus infection.

    “some subjects did have low frequencies of pre-vaccination AIM+ T cells that may be attributed to cross-reactive cells from a prior seasonal coronavirus infection (Grifoni et al., 2020; Figure 1B).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Grifoni et al., 2020 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The T cell response induced by vaccination has a memory subset distribution similar to that after natural SARS-CoV-2 infection and consists mainly of CD45RA− CD27+ memory T cells.

    “These data indicate that the vaccine-elicited T cell response has a similar memory T cell subset distribution to the response generated following SARS-CoV-2 infection and is composed of primarily CD45RA− CD27+ memory T cells.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Prior work reports that vaccination generates memory B cells and antibodies that neutralize SARS-CoV-2, including variants like B.1.351.

    “Recent studies have documented strong memory B cell and antibody responses post-vaccination that neutralize SARS-CoV-2, including variants of concern (VOCs) such as B.1.351 (Beta) (Goel et al., 2021; Krammer et al., 2021; Sahin et al., 2020; Widge et al., 2021).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Goel et al., 2021 source

      Not checked in the free run.

    • cites Krammer et al., 2021 source

      Not checked in the free run.

    • cites Sahin et al., 2020 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    In naive individuals, a rapid antigen-specific CD4+ T cell response, and to a lesser extent CD8+ T cell response, pushes UMAP2 negative after the first dose, while strong humoral immunity pushes UMAP2 positive after the booster in naive individuals and after the first dose in recovered individuals.

    “A rapid antigen-specific CD4+ T cell and, to a lesser extent, CD8+ T cell response drives the UMAP2 coordinate in a negative direction post-primary in naive individuals, whereas robust humoral immunity drives UMAP2 in a positive direction post-boost in naive individuals and post-primary in recovered individuals”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Subtle changes after stimulation might affect precise differentiation state assignment.

    “Although on the basis of our assay optimization studies, the differentiation markers used to separate memory T cell and helper T cell subsets appear to remain stable during the time frame of the AIM assay, it is possible that subtle changes following stimulation might influence precise differentiation state assignment.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Interpretationcitation

    EM1 cells may be memory T cells that survey blood and peripheral tissues, while CM cells can efficiently home to lymphoid tissues.

    “As CCR7 promotes homing to secondary lymphoid tissues, EM1 may represent memory T cells that can survey blood and peripheral tissues, whereas CM can home efficiently to lymphoid tissues (Romero et al., 2007).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The CM and EM1 memory T cell subsets have many shared functional and memory-like features but differ in CCR7 expression.
  • May combine two claims.

    Interpretationreasoning

    mRNA vaccination-induced CD4+ and CD8+ T cell responses will be long lived and able to contribute to future recall responses.

    “Although we await follow-up studies to directly interrogate longevity, the observed induction of memory T cell subsets with capacity for durability by mRNA vaccination supports the hypothesis that vaccine-induced CD4+ and CD8+ T cell responses will be long lived and capable of contributing to future recall responses.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: CM and EM1 memory T cell subsets are longer lived than effector T cells.
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    All statistical tests were two-sided with a nominal significance threshold of p < 0.05.

    “All tests were performed two-sided with a nominal significance threshold of p < 0.05.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The sensitivity of the AIM assay may differ depending on individual immunodominant responses and HLA types.

    “Despite the utility of this approach for capturing the diversity of the T cell response to epitopes throughout the Spike protein and in individuals with diverse HLA allotypes, the sensitivity of the assay may differ on the basis of the individual immunodominant responses and HLA types.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Multiple comparisons were adjusted using Holm correction.

    “In all cases of multiple comparisons, adjustment was performed using Holm correction.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim.

    Premisecitation

    People who have recovered from SARS-CoV-2 infection reach maximum antigen-specific humoral immune responses after only one vaccine dose.

    “Previous studies have demonstrated that individuals who have recovered from SARS-CoV-2 infection achieve maximum antigen-specific humoral immune responses after only a single vaccine dose”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Angyal et al., 2021

      Not checked in the free run.

    • cites Bradley et al., 2021

      Not checked in the free run.

    • cites Camara et al., 2021

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Study design and conductnone given

    Stimulation of T cells may alter surface marker expression.

    “A further limitation is that stimulation of T cells may alter surface marker expression.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Reliable assessments of durable T cell memory require analysis at extended post-vaccination time points that were not available in this study.

    “Reliable assessments of durable T cell memory will require analysis at extended time points post-vaccination that were not available at the time of the study.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim.

    Premisecitation

    CCR7 directs homing to secondary lymphoid tissues.

    “As CCR7 promotes homing to secondary lymphoid tissues, EM1 may represent memory T cells that can survey blood and peripheral tissues, whereas CM can home efficiently to lymphoid tissues (Romero et al., 2007).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Romero et al., 2007 source

      Not checked in the free run.

37 of 37
  • The paper relies on this without support.

    Antibody responses serve as the surrogate of protection for most licensed vaccines.

    “B cells and antibodies are important components of immunological memory, and antibody responses are the surrogate of protection for most licensed vaccines.”
  • The paper relies on this without support.

    The T cell response to mRNA vaccination is less well characterized than the humoral response.

    “The T cell response to mRNA vaccination is less well characterized than the humoral response, though initial reports indicate that T cells, particularly CD4+ T cells, are primed by the vaccine”
  • The paper relies on this without support.

    The details of antigen-specific T cell induction after vaccination are still incompletely understood.

    “However, the details of antigen-specific T cell induction following vaccination remain incompletely understood, and questions remain about the trajectory of the adaptive immune response following vaccination.”
  • The paper relies on this without support.

    It is unclear whether Tfh cells are efficiently primed and whether they relate to vaccine-induced antibodies or memory B cells.

    “For example, it is unclear whether Tfh cells are efficiently primed and whether these cells relate to vaccine-induced antibodies or memory B cells.”
  • The paper relies on this without support.

    It is unclear whether CD4+ and CD8+ T cell priming kinetics differ and how priming compares between SARS-CoV-2-naive and recovered subjects.

    “It is also unclear whether the kinetics of T cell priming differs for CD4+ and CD8+ T cells and how such T cell priming events might compare for SARS-CoV-2-naive versus recovered subjects.”
  • The paper relies on this without support.

    The orchestration of different vaccine-induced immune responses remains incompletely understood.

    “Overall, the orchestration of different vaccine-induced immune responses remains to be fully understood.”
  • The paper relies on this without support.

    The CM and EM1 memory T cell subsets have many shared functional and memory-like features but differ in CCR7 expression.

    “These two subsets share many functional and memory-like attributes but differ in CCR7 expression.”
  • The paper relies on this without support.

    CM and EM1 memory T cell subsets are longer lived than effector T cells.

    “These memory T cell subsets are longer lived compared with effector T cells”
8 of 8

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • mRNA vaccination generates spike-specific memory CD4+ and CD8+ T cell responses.

    “mRNA vaccination has also been shown to generate spike-specific memory CD4+ and CD8+ T cell responses (19–22).”
  • Peak CD4+ T cell responses after SARS-CoV-2 mRNA vaccination were composed predominantly of central memory (CM) and effector memory 1 (EM1) cells in both SARS-CoV-2-naïve and -recovered individuals.

    “Peak CD4+ T cell responses after SARS-CoV-2 mRNA vaccination were composed of predominantly central memory [(CM); CD45RA− CD27+ CCR7+] and effector memory 1 [(EM1); CD45RA− CD27+ CCR7−] cells in both SARS-CoV-2–naïve and –recovered individuals (Fig. 5F) (19).”

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References 61 · Cited by 499

Research works printed but not linked: 6

  1. Bradley, 2021, Antibody responses boosted in seropositive healthcare workers after single dose of SARS-CoV-2 mRNA vaccine, medRxiv
  2. Levi, 2021, A cautionary note on recall vaccination in ex-COVID-19 subjects, medRxiv
  3. Saadat, 2021, Single dose vaccination in healthcare workers previously infected with SARS-CoV-2, medRxiv
  4. Samanovic, 2021, Poor antigen-specific responses to the second BNT162b2 mRNA vaccine dose in SARS-CoV-2-experienced individuals, medRxiv
  5. Tarke, 2021, Negligible impact of SARS-CoV-2 variants on CD4+ and CD8+ T cell reactivity in COVID-19 exposed donors and vaccinees, bioRxiv
  6. Wu, 2020, Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications, medRxiv

Authors
Painter, M. M., Mathew, D., Goel, R. R., Apostolidis, S. A., Pattekar, A., Kuthuru, O., Baxter, A. E., Herati, R. S., Oldridge, D. A., Gouma, S., Hicks, P., Dysinger, S., Lundgreen, K. A., Kuri-Cervantes, L., Adamski, S., Hicks, A., Korte, S., Giles, J. R., Weirick, M. E., McAllister, C. M., Dougherty, J., Long, S., D’Andrea, K., Hamilton, J. T., Betts, M. R., Bates, P., Hensley, S. E., Grifoni, A., Weiskopf, D., Sette, A., Greenplate, A. R., & Wherry, E. J.
Affiliations
  • University of Pennsylvania (US)
  • New York University (US)
  • Parker Institute for Cancer Immunotherapy (US)
  • La Jolla Institute for Immunology (US)
Corresponding author
Wherry, E. John
Venue
Immunity
Publisher
Elsevier BV
Published
2021-09
Volume
54
Issue
9
Pages
2133-2142.e3
ISSN
1074-7613 (ISSN-L)
OpenAlex
W3190606158
Cited by
499
References
61
Citations by year
2026: 41 · 2025: 69 · 2024: 60 · 2023: 112 · 2022: 168 · 2021: 49
FWCI
30.80
Type
journal article
Language
en
Open access
Locations
  • Immunity (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (AI082630, AI155577, AI149680, T32 AI055400, T32 CA009140, AI105343, AI152236, HL143613, AI108545, T32 AR076951-01)
  • Perelman School of Medicine, University of Pennsylvania
  • Parker Institute for Cancer Immunotherapy
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords
COVID-19 mRNA vaccine, CD4+ T cell priming, CD8+ T cell responses, Th1 cells, T follicular helper cells, humoral immunity, neutralizing antibodies, booster vaccination
MeSH terms
COVID-19, SARS-CoV-2, COVID-19 Vaccines, BNT162 Vaccine, 2019-nCoV Vaccine mRNA-1273, CD69 Antigens, Adult, Antibodies, Viral, Antigens, Differentiation, T-Lymphocyte, Female, Humans, Immunity, Cellular, Immunization, Secondary, Immunologic Memory, Lymphocyte Activation, Male, Middle Aged, Peptides, Vaccination, Antigens, CD, CD8-Positive T-Lymphocytes, Th1 Cells, Lectins, C-Type, Young Adult, Immunity, Humoral, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus

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