Robust T Cell Responses to the Pfizer/BioNTech Vaccine Compared to Infection and Evidence of Attenuated CD8 T Cell Responses Due to COVID-19

Gao, Fei; Mallajoysula, Vamsee; Arunachalam, Prabhu S.; Ploeg, Kattria van der; Manohar, Monali; Röltgen, Katharina; Yang, Fan; Wirz, Oliver F.; Hoh, Ramona A.; Haraguchi, Emily; Lee, Ji-Yeun; Willis, Richard A.; Ramachandiran, Vasanthi; Li, Jiefu; Kathuria, Karan R.; Li, Chunfeng; Lee, Alexandra S.; Shah, Mihir; Sindher, Sayantani; González, Joseph C.; Altman, John D.; Wang, Taia T.; Boyd, Scott D.; Pulendran, Bali; Jagannathan, Prasanna; Nadeau, Kari; Davis, Mark David McGregor

doi:10.2139/ssrn.4358842

Cited by 5 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The majority of TCRs in the S-specific cluster mapped to peptides 160 to 218 of S protein (Fig. 1L), which was reported to contain immunodominant CD4 T cell epitopes (39,40). Thus, multimodal single-cell profiling after AIM permits the transcriptional and clonotypic evaluation of Sspecific memory CD4 T cells.…”

Section: S-specific Cd4 T Cells Form a Distinct Cluster In The Aim Assaymentioning

confidence: 91%

“…To identify vaccine-and infection-primed participants' S-specific memory CD4 T cells, we used the activation-induced marker (AIM) assay (12,(35)(36)(37)(38)(39)(40)(41)(42). After overnight stimulation with overlapping S peptides, S-specific CD4 T cells were identified on the basis of the coexpression of activation markers such as CD69, CD137, and CD200 (Fig.…”

Section: S-specific Cd4 T Cells Form a Distinct Cluster In The Aim Assaymentioning

confidence: 99%

See 1 more Smart Citation

SARS-CoV-2 inflammation durably imprints memory CD4 T cells

Gray-Gaillard,

Solis,

Chen

et al. 2024

Sci. Immunol.

View full text Add to dashboard Cite

Memory CD4 T cells are critical to human immunity, yet it is unclear whether viral inflammation during memory formation has long-term consequences. Here, we compared transcriptional and epigenetic landscapes of Spike (S)–specific memory CD4 T cells in 24 individuals whose first exposure to S was via SARS-CoV-2 infection or mRNA vaccination. Nearly 2 years after memory formation, S-specific CD4 T cells established by infection remained enriched for transcripts related to cytotoxicity and for interferon-stimulated genes, likely because of a chromatin accessibility landscape altered by inflammation. Moreover, S-specific CD4 T cells primed by infection had reduced proliferative capacity in vitro relative to vaccine-primed cells. Furthermore, the transcriptional state of S-specific memory CD4 T cells was minimally altered by booster immunization and/or breakthrough infection. Thus, infection-associated inflammation durably imprints CD4 T cell memory, which affects the function of these cells and may have consequences for long-term immunity.

show abstract

Section: S-specific Cd4 T Cells Form a Distinct Cluster In The Aim Assaymentioning

confidence: 91%

Section: S-specific Cd4 T Cells Form a Distinct Cluster In The Aim Assaymentioning

confidence: 99%

SARS-CoV-2 inflammation durably imprints memory CD4 T cells

Gray-Gaillard,

Solis,

Chen

et al. 2024

Sci. Immunol.

View full text Add to dashboard Cite

show abstract

“…4c ). Based on prior data from multimer-sorted T cells with known specificities for Influenza A and B viruses, Cytomegalovirus (CMV), Epstein-Barr virus (EBV) and SARS-CoV-2 respectively 49,50 , new TCR sequence clusters obtained from Long COVID patients and convalescent controls could be mapped to these known specificities ( Fig. 4c ).…”

Section: Resultsmentioning

confidence: 99%

Restrained memory CD8⁺T cell responses favors viral persistence and elevated IgG responses in patients with severe Long COVID

Rodriguez,

Tan,

Lakshmikanth

et al. 2024

Preprint

View full text Add to dashboard Cite

During the COVID-19 pandemic it was widely described that certain individuals infected by SARS-CoV-2 experience persistent disease signs and symptoms, Long COVID, which in some cases is very severe with life changing consequences. To maximize our chances of identifying the underpinnings of this illness, we have focused on 121 of the most severe cases from >1000 patients screened in specialized clinics in Sweden and Belgium. We restricted this study to subjects with objective measures of organ damage or dysfunction, >3 months following a verified, but mild- to-moderate SARS-CoV-2 infection. By performing systems-level immunological testing and comparisons to controls fully convalescent following a similar mild/moderate COVID-19 episode, we identify elevated serological responses to SARS-CoV-2 in severe Long COVID suggestive of chronic antigen stimulation. Persistent viral reservoirs have been proposed in Long COVID and using multiple orthogonal methods for detection of SARS-CoV-2 RNA and protein in plasma we identify a subset of patients with detectable antigens, but with minimal overlap across assays, and no correlation to symptoms or immune measurements. Elevated serologic responses to SARS-CoV-2 on the other hand were inversely correlated with clonally expanded memory CD8+ T cells, indicating that restrained clonal expansion enables viral persistence, chronic antigen exposure and elevated IgG responses, even if antigen-detection in blood is not universally possible.

show abstract

“…Some ME/CFS patients have been reported to have exacerbation of their symptoms following SARS-CoV-2 vaccination ( ANZMES, 2021 ; Johnson, 2022 ; Johnson, 2023 ). A recent study shows that people infected with SARS-CoV-2 prior to vaccination produced spike-specific CD8 T-cells at considerably lower levels—and with more dysfunctional response—than vaccinated people who had never been infected ( Gao et al, 2023 ). Similar to our results, these findings suggest that SARS-CoV-2 infection damages the CD8 T-cell response, an effect similar to that observed in previous studies showing long-term damage to the immune system after infection with hepatitis C or HIV1, both persistent viruses that can induce T-cell clonal exhaustion ( McLane et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of CD8 T-cell dysfunction associated with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID and treatment with a nebulized antioxidant/anti-pathogen agent in a retrospective case series

Gil,

Hoag,

Salerno

et al. 2024

Brain, Behavior, & Immunity - Health

View full text Add to dashboard Cite

Robust T Cell Responses to the Pfizer/BioNTech Vaccine Compared to Infection and Evidence of Attenuated CD8 T Cell Responses Due to COVID-19

Cited by 5 publications

References 0 publications

SARS-CoV-2 inflammation durably imprints memory CD4 T cells

SARS-CoV-2 inflammation durably imprints memory CD4 T cells

Restrained memory CD8⁺T cell responses favors viral persistence and elevated IgG responses in patients with severe Long COVID

Identification of CD8 T-cell dysfunction associated with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID and treatment with a nebulized antioxidant/anti-pathogen agent in a retrospective case series

Contact Info

Product

Resources

About

Robust T Cell Responses to the Pfizer/BioNTech Vaccine Compared to Infection and Evidence of Attenuated CD8 T Cell Responses Due to COVID-19

Cited by 5 publications

References 0 publications

SARS-CoV-2 inflammation durably imprints memory CD4 T cells

SARS-CoV-2 inflammation durably imprints memory CD4 T cells

Restrained memory CD8+T cell responses favors viral persistence and elevated IgG responses in patients with severe Long COVID

Identification of CD8 T-cell dysfunction associated with symptoms in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Long COVID and treatment with a nebulized antioxidant/anti-pathogen agent in a retrospective case series

Contact Info

Product

Resources

About

Restrained memory CD8⁺T cell responses favors viral persistence and elevated IgG responses in patients with severe Long COVID