Rapid induction of antigen-specific CD4+ T cells is associated with coordinated humoral and cellular immunity to SARS-CoV-2 mRNA vaccination
Open accessAbstract
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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- 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
- Findingown data
Vaccine-induced Th1 cell responses after the first dose correlate with post-boost CD8+ T cell responses in SARS-CoV-2-naive individuals.
“Vaccine-induced Th1 and Tfh cell responses following the first dose correlated with post-boost CD8+ T cells and neutralizing antibodies, respectively.”
- Also stated in: § Antigen-specific Th1 and cTfh cells induced by the first dose correlate with CD8+ T cell and humoral responses to the second dose · boosted
“we observed a strong correlation between the frequency of pre-boost AIM+ Th1 cells and the frequency of post-boost AIM+ CD8+ T cells in SARS-CoV-2-naive individuals”
Quote in the paperSubstantial claim - Also stated in: § Antigen-specific Th1 and cTfh cells induced by the first dose correlate with CD8+ T cell and humoral responses to the second dose · boosted
- Findingown data
UMAP1 reflects the magnitude of the anti-SARS-CoV-2 immune response to vaccination.
“Correlating individual antigen-specific features with the UMAP coordinates revealed that UMAP1 is a measure of the anti-SARS-CoV-2 immune response to vaccination”
Quote in the paperSubstantial claim - Findingown data
In naive individuals, the first dose mainly induced AIM+ CD4+ T cells with EM1 and CM phenotypes, resembling the response in recovered donors.
“In SARS-CoV-2-naive individuals, the first dose of vaccine primarily induced AIM+ CD4+ T cells in the EM1 and CM subsets, similar to the response in recovered donors”
Quote in the paperSubstantial claim - Findingown data
Vaccination did not substantially alter the memory subset distribution of these SARS-CoV-2-specific CD4+ T cells.
“The memory T cell subset distribution of these SARS-CoV-2-specific CD4+ T cells did not change substantially following vaccination”
Quote in the paperSubstantial claim - Findingown data
Recovered subjects had a smaller fraction of AIM+ EM2 and EM3 CD8+ T cells at baseline.
“A smaller proportion of AIM+ EM2 and EM3 CD8+ T cells was observed at baseline in recovered subjects.”
Quote in the paperNot a substantial claim - Findingown data
Before vaccination, many SARS-CoV-2-naive individuals had no detectable response to peptide stimulation.
“pre-vaccination responses to peptide stimulation were undetectable in many SARS-CoV-2-naive individuals”
Quote in the paperSubstantial claim - Findingown data
Correlations among key antigen-specific parameters over time showed relationships between post-primary and post-boost immunity within and across adaptive immune arms.
“correlations of key antigen-specific parameters of the vaccine response over time revealed relationships between post-primary and post-boost immunity within and between arms of the adaptive immune system”
Quote in the paperSubstantial claim - Findingown data
T cell responses to mRNA vaccination did not correlate with age.
“T cell responses upon mRNA vaccination were not correlated with age”
- Also stated in: § Discussion · plain
“substantial age-associated changes in the induction of antigen-specific T cell responses were not observed.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
In this study, vaccine-induced CD4+ and CD8+ T cells specific to SARS-CoV-2 resembled baseline memory T cell responses from natural SARS-CoV-2 infection in quality.
“Vaccine-induced CD4+ and CD8+ T cells specific for SARS-CoV-2 were qualitatively similar to baseline memory T cell responses generated following natural SARS-CoV-2 infection and mainly mapped to CM and EM1 memory T cell subsets.”
Quote in the paperSubstantial claim - Findingown data
Apart from EMRA cells, the antigen-specific AIM+ CD8+ T cell response after vaccination in naive donors looked like that in recovered donors.
“With the exception of the EMRA population, the antigen-specific AIM+ CD8+ T cell response in SARS-CoV-2-naive donors following vaccination resembled that observed in recovered donors”
Quote in the paperSubstantial claim - Findingown data
Naive subjects had a more dynamic trajectory: UMAP1 rose and UMAP2 fell at time points 2 and 3, then both converged upward after the second dose.
“In SARS-CoV-2-naive subjects there was a more dynamic trajectory over time with an initial increase in UMAP1 and decrease in UMAP2 signal at time points 2 and 3, followed by a coalescence toward increased UMAP1 and UMAP2 after the second vaccine dose”
Quote in the paperSubstantial claim - Findingown data
In naive subjects, the first dose also mainly produced antigen-specific Th1 and cTfh cells.
“In SARS-CoV-2-naive subjects, the first vaccine dose also elicited predominantly antigen-specific Th1 and cTfh cells”
Quote in the paperSubstantial claim - Findingown data
UMAP1 also showed a signal of prior SARS-CoV-2 infection, since recovered subjects had higher UMAP1 values at baseline.
“UMAP1 also revealed a signal of previous SARS-CoV-2 infection, as recovered subjects occupied a location with increased UMAP1 signal at baseline”
Quote in the paperNot a substantial claim - Findingown data
The ratio of Th1 to cTfh among AIM+ cells before boosting did not correlate with post-boost humoral or CD8+ T cell responses.
“the pre-boost Th1/cTfh ratio within the AIM+ cells did not correlate with post-boost humoral or CD8+ T cell responses”
Quote in the paperSubstantial claim - Findingown data
Naive individuals had few AIM+ EMRA CD8+ T cells at any time point.
“in SARS-CoV-2-naive individuals, few AIM+ EMRA CD8+ T cells were observed at any time point”
Quote in the paperNot a substantial claim - Findingown data
In recovered individuals, the baseline AIM+ CD4+ T cell response was dominated by cTfh and Th1 cells.
“The baseline AIM+ CD4+ T cell response in recovered individuals, however, was dominated by cTfh and Th1 cells”
Quote in the paperSubstantial claim - Findingown data
Vaccine-induced cTfh cell responses after the first dose correlate with post-boost neutralizing antibody titers against D614G and B.1.351 in SARS-CoV-2-naive individuals.
“Vaccine-induced Th1 and Tfh cell responses following the first dose correlated with post-boost CD8+ T cells and neutralizing antibodies, respectively.”
- Also stated in: § Antigen-specific Th1 and cTfh cells induced by the first dose correlate with CD8+ T cell and humoral responses to the second dose · plain
“the frequency of pre-boost antigen-specific cTfh cells correlated with post-boost neutralizing antibody titers against both the dominant strain of SARS-CoV-2 (D614G, dominant at the time of study) and the Beta variant (B.1.351)”
Quote in the paperSubstantial claim - Also stated in: § Antigen-specific Th1 and cTfh cells induced by the first dose correlate with CD8+ T cell and humoral responses to the second dose · plain
- Findingown data
At baseline, most donors who had recovered from SARS-CoV-2 had readily detectable antigen-specific CD4+ and CD8+ T cells.
“most SARS-CoV-2-recovered donors had clearly detectable antigen-specific CD4+ and CD8+ T cell populations at baseline”
Quote in the paperNot a substantial claim - Findingown data
AIM+ CD8+ T cells showed a memory subset distribution similar to that of AIM+ CD4+ T cells.
“AIM+ CD8+ T cells had a similar subset distribution to AIM+ CD4+ T cells.”
Quote in the paperSubstantial claim - Findingown data
The analysis also highlights pre-boost features such as cTfh and Th1 that correlate with post-boost humoral and cellular responses.
“This analysis also highlights pre-boost immune response features such as cTfh and Th1 that correlate with post-boost humoral and cellular responses”
Quote in the paperSubstantial claim - Findingown data
After the first dose, only 24 of 34 naive subjects (71%) had detectable antigen-specific CD8+ T cell responses.
“Only 24 of 34 SARS-CoV-2-naive subjects (71%) generated detectable antigen-specific CD8+ T cell responses following the first dose.”
Quote in the paperSubstantial claim - Findingown data
UMAP2 reflects the relative balance between humoral and cellular immunity, particularly CD4+ T cell responses.
“UMAP2 captures the relative balance between humoral and cellular immune responses, especially CD4+ T cell responses”
Quote in the paperSubstantial claim - Findingown data
In SARS-CoV-2-naive individuals, mRNA vaccination elicits rapid antigen-specific CD4+ T cell responses after the first dose.
“Vaccination induced rapid antigen-specific CD4+ T cell responses in naive subjects after the first dose”
- Also stated in: § Antigen-specific CD4+ T cell responses to the first vaccine dose are boosted by the second dose in SARS-CoV-2-naive individuals · plain
“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”
- Also stated in: § Introduction · plain
“All SARS-CoV-2-naive subjects mounted robust CD4+ T cell responses following the first vaccine dose”
Quote in the paperSubstantial claim - Also stated in: § Antigen-specific CD4+ T cell responses to the first vaccine dose are boosted by the second dose in SARS-CoV-2-naive individuals · plain
- Findingown data
After the booster, 29 of 33 naive individuals (88%) had CD8+ T cell responses above their own pre-vaccine baseline.
“29 of 33 SARS-CoV-2-naive individuals (88%) had post-boost CD8+ T cell responses that were detectable above their individual pre-vaccine baseline”
Quote in the paperSubstantial claim - Findingown data
At baseline in recovered subjects, the antigen-specific CD8+ T cell response had similar proportions of EM1, CM, and terminally differentiated EMRA cells.
“The baseline antigen-specific CD8+ T cell response in recovered subjects was composed of similar proportions of EM1, CM, and terminally differentiated CD8+ EMRA (CD45RA+ CD27− CCR7−) T cells”
Quote in the paperNot a substantial claim - Findingown data
UMAP1 captured a coordinated response in which antigen-specific CD8+ T cells and CD4+ Th1 and cTfh cells rose together with antibodies, IgG+ memory B cells, RBD-focused humoral responses, and neutralizing titers.
“UMAP1 captured a coordinated immune response in which antigen-specific CD8+ T cells and CD4+ Th1 and cTfh cells were increased coordinately with antibodies, IgG+ memory B cells, RBD-focused humoral responses, and increased neutralizing antibody titers”
Quote in the paperSubstantial claim - Findingown data
In SARS-CoV-2-recovered subjects, the immune landscape is relatively stable after the second vaccine dose.
“Moreover, an integrated analysis of 26 antigen-specific features of the immune response to vaccination highlighted the immunological benefit of the first dose in recovered subjects while also illustrating the relative stability of the immune landscape in response to the second vaccine dose.”
Quote in the paperSubstantial claim - Findingown data
Pre-boost cTfh cells correlate with post-boost neutralizing antibody responses.
“The notion that early CD4+ T cell responses have a functional role in immunity is also supported by the correlation between pre-boost Th1 and cTfh cells with post-boost CD8+ T cell and neutralizing antibody responses, respectively.”
Quote in the paperSubstantial claim - Findingown data
Pre-boost cTfh cells were better predictors of post-boost humoral responses than many pre-boost humoral immunity readouts.
“When examining multiple individual antigen-specific responses over time, pre-boost cTfh were better predictors of post-boost humoral responses than many pre-boost readouts of humoral immunity, pointing to the critical role of Tfh in coordinating humoral immunity.”
Quote in the paperSubstantial claim - Findingown data
Pre-boost antigen-specific cTfh cells correlate with post-boost memory B cell responses.
“In addition to strongly correlating with post-boost neutralizing antibody titers, pre-boost antigen-specific cTfh cells also correlated with post-boost memory B cell responses.”
Quote in the paperSubstantial claim - Findingown data
Pre-boost antigen-specific Th1 cells correlated with post-boost CD8+ T cell responses as strongly as pre-boost CD8+ T cells did.
“Likewise, pre-boost antigen-specific Th1 cells were as strongly correlated with post-boost CD8+ T cell responses as pre-boost CD8+ T cells.”
Quote in the paperSubstantial claim - Findingown data
Pre-boost antigen-specific cTfh cells strongly correlate with post-boost neutralizing antibody titers.
“In addition to strongly correlating with post-boost neutralizing antibody titers, pre-boost antigen-specific cTfh cells also correlated with post-boost memory B cell responses.”
Quote in the paperSubstantial claim - Findingown data
In SARS-CoV-2-recovered subjects, the second vaccine dose has minimal effect on the magnitude, memory phenotype, or helper subset distribution of antigen-specific CD4+ or CD8+ T cell responses.
“Our present studies now provide information on both CD4+ and CD8+ T cell responses in naive and recovered subjects and support the idea that the second dose of vaccine has minimal impact on the magnitude, memory phenotype, or helper subset distribution of antigen-specific CD4+ or CD8+ T cell responses in SARS-CoV-2-recovered subjects.”
Quote in the paperSubstantial claim - Findingown data
In this study, antigen-specific CD8+ T cells developed gradually.
“This observation may be noteworthy given the gradual development of antigen-specific CD8+ T cells observed here and the previous observations for humoral responses (Goel et al., 2021; Jackson et al., 2020), which only consistently reach maximal levels after the second vaccine dose.”
Quote in the paperSubstantial claim - Findingown data
No decrease in T cell responses with age was observed.
“Although we observed no decrease in T cell responses with age, the cohort examined here had relatively few participants of advanced age, necessitating larger follow-up studies.”
Quote in the paperNot a substantial claim - Findingown data
In SARS-CoV-2-naive subjects, the antigen-specific immune response showed robust and dynamic change in coordination and evolution after both the first and second vaccine doses.
“In contrast, in SARS-CoV-2-naive subjects, there was robust and dynamic change in the coordination and evolution of the antigen-specific immune response following the first as well as the second vaccine dose.”
Quote in the paperSubstantial claim - Findingown data
Pre-boost Th1 cells correlate with post-boost CD8+ T cell responses.
“The notion that early CD4+ T cell responses have a functional role in immunity is also supported by the correlation between pre-boost Th1 and cTfh cells with post-boost CD8+ T cell and neutralizing antibody responses, respectively.”
Quote in the paperSubstantial claim - Findingown data
In SARS-CoV-2-naive individuals, the first vaccine dose rapidly and universally induced SARS-CoV-2-specific CD4+ T cells.
“One key observation was the rapid and universal induction of SARS-CoV-2-specific CD4+ T cells following the first vaccine dose in SARS-CoV-2-naive individuals.”
Quote in the paperSubstantial claim - Findingown data
In this study, vaccine-induced CD4+ and CD8+ T cells specific to SARS-CoV-2 were mostly found in the CM and EM1 memory T cell subsets.
“Vaccine-induced CD4+ and CD8+ T cells specific for SARS-CoV-2 were qualitatively similar to baseline memory T cell responses generated following natural SARS-CoV-2 infection and mainly mapped to CM and EM1 memory T cell subsets.”
Quote in the paperSubstantial claim - Interpretationcitation
Memory CD4+ and CD8+ T cells specific for antigen are probably less vulnerable to antibody escape mutations in viral variants because T cells can recognize epitopes across the Spike protein.
“antigen-specific memory CD4+ and CD8+ T cells are likely to be less affected by antibody escape mutations in variant viral strains, as T cells can recognize peptide epitopes distributed throughout the SARS-CoV-2 Spike protein (Angyal et al., 2021; Tarke et al., 2021b; Woldemeskel et al., 2021).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Angyal et al., 2021
Not checked in the free run.
- cites Tarke et al., 2021b
Not checked in the free run.
- cites Woldemeskel et al., 2021 source
Not checked in the free run.
- Study design and conductown data
These separate marker strategies for AIM+ CD4+ and CD8+ T cells gave the best detection of vaccine-induced responses compared with background in unstimulated controls.
“These distinct approaches for defining AIM+ CD4+ and CD8+ T cells provided optimal detection of vaccine-elicited responses relative to background signals in unstimulated controls”
Quote in the paperSubstantial claim - Interpretationown data
These data suggest a potential benefit of two-dose vaccination: CD4+ T cells primed by the first dose may enhance and coordinate responses after the booster.
“these data highlight one of the potential benefits of a two-dose vaccination regimen, whereby CD4+ T cells primed by the first vaccine dose may augment and coordinate responses following the booster vaccination.”
Quote in the paperSubstantial claim - Interpretationown data
This unbiased integrated analysis of 26 antigen-specific responses illustrates the coordinated immunological basis of mRNA vaccine-induced immunity.
“this unbiased integrated analysis of 26 antigen-specific immune responses illustrates the coordinated immunological underpinnings of the immunity induced by mRNA vaccines.”
Quote in the paperSubstantial claim - Study design and conductown data
AIM+ CD4+ and CD8+ T cell frequencies correlated strongly with activated Ki67+CD38+ T cell frequencies after each dose.
“We further confirmed that the frequency of AIM+ CD4+ and CD8+ T cells correlated strongly with the frequency of activated Ki67+CD38+ T cells (Figure S1D), another method for quantifying antigen-specific responses, after each vaccine dose”
Quote in the paperNot a substantial claim - Study design and conductcitation
The AIM assay accurately detects cTfh that are known to contain antigen-specific T cells in other contexts.
“indicating that the AIM assay accurately captures cTfh known to contain antigen-specific T cells in other settings (Herati et al., 2017).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Herati et al., 2017 source
Not checked in the free run.
- Study design and conductown data
Other AIM marker combinations showed similar kinetics of antigen-specific T cell responses, though sometimes with higher background.
“Alternative combinations of AIMs revealed similar kinetics of antigen-specific T cell responses, though in some cases with higher background”
Quote in the paperNot a substantial claim - Interpretationown data
CD4+ T cells primed quickly by the first dose help coordinate the response to the second dose in naive 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.”
- Also stated in: § Antigen-specific Th1 and cTfh cells induced by the first dose correlate with CD8+ T cell and humoral responses to the second dose · hedged
“these data highlight one of the potential benefits of a two-dose vaccination regimen, whereby CD4+ T cells primed by the first vaccine dose may augment and coordinate responses following the booster vaccination.”
Quote in the paperSubstantial claim - Also stated in: § Antigen-specific Th1 and cTfh cells induced by the first dose correlate with CD8+ T cell and humoral responses to the second dose · hedged
- Premisecitation
Some individuals with inherited or treatment-related B cell deficiencies who did not produce neutralizing antibodies still recovered from COVID-19.
“patients who failed to develop neutralizing antibodies, in some cases because of inherited or treatment-induced B cell deficiencies, have recovered from COVID-19 (Soresina et al., 2020; Wu et al., 2020; Wurm et al., 2020).”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationreasoning
A prime-boost strategy amplifies a coordinated vaccine-induced immune response.
“These findings suggest that the CD4+ T cell response generated by the first vaccine dose guides multiple arms of the adaptive immune response to booster vaccination and highlight the benefits of a prime-boost strategy to amplify a coordinated vaccine-induced immune response.”
Quote in the paperSubstantial claim - Interpretationreasoning
Rapid induction of antigen-specific CD4+ T cells after a single vaccine dose may explain the disconnect between low neutralizing responses and vaccine-induced protective immunity following the first dose.
“Indeed, CD4+ T cells can prevent symptomatic SARS-CoV infection in animal models (Zhao et al., 2016), and the rapid induction of antigen-specific CD4+ T cells after only a single vaccine dose may explain the disconnect between low neutralizing responses and vaccine-induced protective immunity following the first dose.”
Quote in the paperSubstantial claim - Study design and conductnone given
The cohort examined here had relatively few participants of advanced age.
“Although we observed no decrease in T cell responses with age, the cohort examined here had relatively few participants of advanced age, necessitating larger follow-up studies.”
Quote in the paperSubstantial claim - Interpretationown data
Early CD4+ T cell responses have a functional role in immunity.
“The notion that early CD4+ T cell responses have a functional role in immunity is also supported by the correlation between pre-boost Th1 and cTfh cells with post-boost CD8+ T cell and neutralizing antibody responses, respectively.”
Quote in the paperSubstantial claim - Interpretationreasoning
Early induction of antigen-specific CD4+ T cells may contribute to the protection seen in clinical trials as early as two weeks after the first vaccine dose.
“These data point to the early induction of antigen-specific CD4+ T cells as a possible contributor to the protection observed in clinical trials as early as two weeks after the first vaccine dose (Baden et al., 2021; Polack et al., 2020), when neutralizing antibody titers are still low in many individuals (Goel et al., 2021).”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationreasoning
The vaccine-elicited immune response is specifically focused on key hallmarks of long-term antiviral immunity.
“In concert with robust humoral immunity, the preferential induction of Th1, Tfh, and CM-like T cells indicates that the vaccine-elicited immune response is specifically focused on the key hallmarks of long-term antiviral immunity that are likely to confer lasting protection against SARS-CoV-2 infection.”
Quote in the paperSubstantial claim- Rests on an assumption: CM and EM1 memory T cell subsets are longer lived than effector T cells.
- Interpretationreasoning
The CD4+ T cell response from the first vaccine dose guides multiple arms of the adaptive immune response to booster vaccination.
“These findings suggest that the CD4+ T cell response generated by the first vaccine dose guides multiple arms of the adaptive immune response to booster vaccination and highlight the benefits of a prime-boost strategy to amplify a coordinated vaccine-induced immune response.”
Quote in the paperSubstantial claim - Study design and conductown data
Based on assay optimization studies, the differentiation markers used to separate memory T cell and helper T cell subsets appear stable during the AIM assay time frame.
“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 - Premisecitation
CD4+ T cells can prevent symptomatic SARS-CoV infection in animal models.
“Indeed, CD4+ T cells can prevent symptomatic SARS-CoV infection in animal models (Zhao et al., 2016), and the rapid induction of antigen-specific CD4+ T cells after only a single vaccine dose may explain the disconnect between low neutralizing responses and vaccine-induced protective immunity following the first dose.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Zhao et al., 2016 source
Not checked in the free run.
- Study design and conductreasoning
The nature of the cohort limits the scope of these findings.
“The scope of these findings is limited by the nature of the cohort.”
Quote in the paperNot a substantial claim - Study design and conductown data
All recovered participants in this study had mild disease.
“In particular, all of the recovered participants in this study experienced mild disease, and it is unclear how mRNA vaccination would affect immune responses in those who have recovered from severe COVID-19.”
Quote in the paperNot a substantial claim - Premisecitation
Humoral responses only consistently reach maximal levels after the second vaccine dose.
“This observation may be noteworthy given the gradual development of antigen-specific CD8+ T cells observed here and the previous observations for humoral responses (Goel et al., 2021; Jackson et al., 2020), which only consistently reach maximal levels after the second vaccine dose.”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationown data
Tfh cells play a critical role in coordinating humoral immunity.
“When examining multiple individual antigen-specific responses over time, pre-boost cTfh were better predictors of post-boost humoral responses than many pre-boost readouts of humoral immunity, pointing to the critical role of Tfh in coordinating humoral immunity.”
Quote in the paperSubstantial claim - Premisecitation
Two weeks after the first vaccine dose, neutralizing antibody titers remain low in many individuals.
“These data point to the early induction of antigen-specific CD4+ T cells as a possible contributor to the protection observed in clinical trials as early as two weeks after the first vaccine dose (Baden et al., 2021; Polack et al., 2020), when neutralizing antibody titers are still low in many individuals (Goel et al., 2021).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Goel et al., 2021 source
Not checked in the free run.
- Interpretationreasoning
These hallmarks are likely to confer lasting protection against SARS-CoV-2 infection.
“In concert with robust humoral immunity, the preferential induction of Th1, Tfh, and CM-like T cells indicates that the vaccine-elicited immune response is specifically focused on the key hallmarks of long-term antiviral immunity that are likely to confer lasting protection against SARS-CoV-2 infection.”
Quote in the paperNot a substantial claim- Rests on an assumption: CM and EM1 memory T cell subsets are longer lived than effector T cells.
- Interpretationreasoning
Access to secondary lymphoid tissues may enable CM cells to contribute to recall responses after booster vaccination or future infection.
“These memory T cell subsets are longer lived compared with effector T cells, and access to secondary lymphoid tissues may allow CM cells to contribute to recall responses upon booster vaccination or future infection.”
Quote in the paperSubstantial claim- Rests on an assumption: CM and EM1 memory T cell subsets are longer lived than effector T cells.
- 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 dataIn 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 claimMay combine two claims.
Findingown dataA 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- Also stated in: § Introduction · plain
May combine two claims.
Findingown dataIn 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 claimMay combine two claims.
Findingown dataTotal 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 claimMay combine two claims.
Findingown dataCD8+ 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- Also stated in: § Prime-boost vaccination induces antigen-specific CD8+ T cells in most SARS-CoV-2-naive individuals · plain
May combine two claims.
Findingown dataPre-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 claimMay combine two claims.
Findingown dataTotal 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 claimMay combine two claims.
Findingown dataA 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 claimMay combine two claims.
Findingown dataIn 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 claimMay combine two claims.
Findingown dataThe 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 claimMay combine two claims.
Findingown dataIn 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 claimMay combine two claims.
Findingown dataAbout 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 claimMay combine two claims.
Findingown dataThe 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 claimMay combine two claims. The quote only partly states this claim.
Findingown dataAn 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- 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
May combine two claims.
Findingown dataIn 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 claimMay combine two claims.
Interpretationown dataOur 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 claimMay combine two claims.
Interpretationown dataThese 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 claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationWhether 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 checkedMay combine two claims.
Interpretationown dataThe 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 claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationTfh 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 checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataEach 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 claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationIn 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.
InterpretationcitationStrong 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 checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSome 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 dataThe 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 claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPrior 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 checkedMay combine two claims.
Interpretationown dataIn 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 claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoningSubtle 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 claimMay combine two claims.
InterpretationcitationEM1 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.
InterpretationreasoningmRNA 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 givenAll 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 claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe 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 claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenMultiple comparisons were adjusted using Holm correction.
“In all cases of multiple comparisons, adjustment was performed using Holm correction.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
PremisecitationPeople 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 givenStimulation 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 claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataReliable 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 claimClassified as probably not a substantial claim.
PremisecitationCCR7 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.
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”
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).”
From mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern (2021) · cites this paper as [19]
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).”
From mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern (2021) · cites this paper as [19]
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No citation lists for this paper yet — checked again daily.
References 61 · Cited by 499
Research works printed but not linked: 6
- Bradley, 2021, Antibody responses boosted in seropositive healthcare workers after single dose of SARS-CoV-2 mRNA vaccine, medRxiv
- Levi, 2021, A cautionary note on recall vaccination in ex-COVID-19 subjects, medRxiv
- Saadat, 2021, Single dose vaccination in healthcare workers previously infected with SARS-CoV-2, medRxiv
- Samanovic, 2021, Poor antigen-specific responses to the second BNT162b2 mRNA vaccine dose in SARS-CoV-2-experienced individuals, medRxiv
- Tarke, 2021, Negligible impact of SARS-CoV-2 variants on CD4+ and CD8+ T cell reactivity in COVID-19 exposed donors and vaccinees, bioRxiv
- 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
- ORCID
- Painter, Mark M.
- Mathew, Divij
- Goel, Rishi R.
- Apostolidis, Sokratis A.
- Pattekar, Ajinkya
- Kuthuru, Oliva
- Baxter, Amy E.
- Herati, Ramin S.
- Oldridge, Derek A.
- Gouma, Sigrid
- Hicks, Philip
- Dysinger, Sarah
- Lundgreen, Kendall A.
- Kuri-Cervantes, Leticia
- Adamski, Sharon
- Hicks, Amanda
- Korte, Scott
- Giles, Josephine R.
- Weirick, Madison E.
- McAllister, Christopher M.
- Dougherty, Jeanette
- Long, Sherea
- Hamilton, Jacob T.
- Betts, Michael R.
- Bates, Paul
- Hensley, Scott E.
- Grifoni, Alba
- Weiskopf, Daniela
- Sette, Alessandro
- Greenplate, Allison R.
- Wherry, E. John
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2021-09
- Volume
- 54
- Issue
- 9
- Pages
- 2133-2142.e3
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC8361141
- 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
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 378 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- 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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