Vaccination reshapes the virus-specific T cell repertoire in unexposed adults

Pan, Yi-Gen; Aiamkitsumrit, Benjamas; Bartolo, Laurent; Wang, Yifeng; Lavery, Criswell; Marc, Adam; Holec, Patrick V.; Rappazzo, C. Garrett; Eilola, Theresa; Gimotty, Phyllis A.; Hensley, Scott E.; Antia, Rustom; Zarnitsyna, Veronika I.; Birnbaum, Michael E.; Su, Laura F.

doi:10.1016/j.immuni.2021.04.023

Cited by 22 publications

(22 citation statements)

References 56 publications

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“…This indicates that in high-quality responders, pre-existing memory clones are surpassed by multiple strongly expanding low-frequency precursors, most likely from the naive pool. A similar clonal hierarchy shift was recently demonstrated for yellow fever vaccination (Pan et al, 2021). In contrast, individuals where pre-existing memory clonotypes remained dominant after vaccination displayed rather poor responses and a lower TCR diversity, as previously shown in mice (Cornberg et al, 2006).…”

Section: Discussionsupporting

confidence: 82%

“…Technical limitations in tracking rare antigen-specific T cells in unexposed individuals have restricted the study of the effect of the pre-vaccination repertoire on the immune-response quality. Rare cell-enrichment approaches allow identification of naive and memory T cells in the pre-exposure repertoire (Bacher et al, , 2016(Bacher et al, , 2019(Bacher et al, , 2020Moon et al, 2007;Obar et al, 2008;Pan et al, 2021;Su et al, 2013). Without enrichment, the detection is mainly restricted to high-frequency memory T cells and only in a variable fraction of unexposed donors Braun et al, 2020;Grifoni et al, 2020;Loyal et al, 2021;Mateus et al, 2021;Ogbe et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…While the importance of the naive compartment is well accepted, the in vivo contribution of pre-existing memory cells is not clear (Lipsitch et al, 2020;Moss, 2022;Woodland and Blackman, 2006). Pre-existing memory T cells have been described for SARS-CoV-2 (Bacher et al, 2020;Bartolo et al, 2021;Braun et al, 2020;Le Bert et al, 2020;Loyal et al, 2021;Mateus et al, 2020;Nelde et al, 2020), but also for many other pathogens Campion et al, 2014;Kwok et al, 2012;Pan et al, 2021;Su et al, 2013). Conflicting data exists regarding the age-associated prevalence of SARS-CoV-2reactive pre-existing memory T cells (Bacher et al, 2020;Dowell et al, 2022;Loyal et al, 2021;Saletti et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…T cell cross-reactivity of these pre-existing SARS-CoV-2-reactive memory cells to related ''common cold'' corona viruses (CCCoVs) (Braun et al, 2020;Low et al, 2021;Loyal et al, 2021;Mateus et al, 2020;Nelde et al, 2020), but also other pathogens, has been described (Bacher et al, 2020;Bartolo et al, 2021;Stervbo et al, 2020;Tan et al, 2021). Importantly, pre-existing T cell memory against so far unexposed antigens is a common phenomenon for many antigens Campion et al, 2014;Kwok et al, 2012;Pan et al, 2021;Su et al, 2013). So far, it is still not clear to what extent pre-existing memory T cells contribute to the immune response against SARS-CoV-2 and how they influence the response quality.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The pre-exposure SARS-CoV-2-specific T cell repertoire determines the quality of the immune response to vaccination

et al. 2022

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The pre-exposure SARS-CoV-2-specific T cell repertoire determines the quality of the immune response to vaccination

et al. 2022

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“…Pre-existing memory T cells can be activated by cross-reactive peptide-targets ( 63 ), making response to immunization to be largely driven by individual immunological history ( 64 ). For instance, a study with yellow fever virus showed that T cell kinetics after vaccination depended on the pre-vaccination precursor frequencies and initial differentiation states ( 65 ). Their results indicate that vaccines re-prioritize the immune repertoire to more relevant T cells against the novel pathogen.…”

Section: Discussionmentioning

confidence: 99%

Large-Scale Structure-Based Screening of Potential T Cell Cross-Reactivities Involving Peptide-Targets From BCG Vaccine and SARS-CoV-2

et al. 2022

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Although not being the first viral pandemic to affect humankind, we are now for the first time faced with a pandemic caused by a coronavirus. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been responsible for the COVID-19 pandemic, which caused more than 4.5 million deaths worldwide. Despite unprecedented efforts, with vaccines being developed in a record time, SARS-CoV-2 continues to spread worldwide with new variants arising in different countries. Such persistent spread is in part enabled by public resistance to vaccination in some countries, and limited access to vaccines in other countries. The limited vaccination coverage, the continued risk for resistant variants, and the existence of natural reservoirs for coronaviruses, highlight the importance of developing additional therapeutic strategies against SARS-CoV-2 and other coronaviruses. At the beginning of the pandemic it was suggested that countries with Bacillus Calmette-Guérin (BCG) vaccination programs could be associated with a reduced number and/or severity of COVID-19 cases. Preliminary studies have provided evidence for this relationship and further investigation is being conducted in ongoing clinical trials. The protection against SARS-CoV-2 induced by BCG vaccination may be mediated by cross-reactive T cell lymphocytes, which recognize peptides displayed by class I Human Leukocyte Antigens (HLA-I) on the surface of infected cells. In order to identify potential targets of T cell cross-reactivity, we implemented an in silico strategy combining sequence-based and structure-based methods to screen over 13,5 million possible cross-reactive peptide pairs from BCG and SARS-CoV-2. Our study produced (i) a list of immunogenic BCG-derived peptides that may prime T cell cross-reactivity against SARS-CoV-2, (ii) a large dataset of modeled peptide-HLA structures for the screened targets, and (iii) new computational methods for structure-based screenings that can be used by others in future studies. Our study expands the list of BCG peptides potentially involved in T cell cross-reactivity with SARS-CoV-2-derived peptides, and identifies multiple high-density “neighborhoods” of cross-reactive peptides which could be driving heterologous immunity induced by BCG vaccination, therefore providing insights for future vaccine development efforts.

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Distinct and dynamic activation profiles of circulating dendritic cells and monocytes in mild COVID‐19 and after yellow fever vaccination

Winheim¹,

Eser

Deák

et al. 2022

Eur J Immunol

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Dysregulation of the myeloid cell compartment is a feature of severe disease in hospitalized COVID‐19 patients. Here, we investigated the response of circulating dendritic cell (DC) and monocyte subpopulations in SARS‐CoV‐2 infected outpatients with mild disease and compared it to the response of healthy individuals to yellow fever vaccine virus YF17D as a model of a well‐coordinated response to viral infection. In SARS‐CoV‐2‐infected outpatients circulating DCs were persistently reduced for several weeks whereas after YF17D vaccination DC numbers were decreased temporarily and rapidly replenished by increased proliferation until 14 days after vaccination. The majority of COVID‐19 outpatients showed high expression of CD86 and PD‐L1 in monocytes and DCs early on, resembling the dynamic after YF17D vaccination. In a subgroup of patients, low CD86 and high PD‐L1 expression were detected in monocytes and DCs coinciding with symptoms, higher age, and lower lymphocyte counts. This phenotype was similar to that observed in severely ill COVID‐19 patients, but less pronounced. Thus, prolonged reduction and dysregulated activation of blood DCs and monocytes were seen in a subgroup of symptomatic non‐hospitalized COVID‐19 patients while a transient coordinated activation was characteristic for the majority of patients with mild COVID‐19 and the response to YF17D vaccination.

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Vaccination reshapes the virus-specific T cell repertoire in unexposed adults

Cited by 22 publications

References 56 publications

The pre-exposure SARS-CoV-2-specific T cell repertoire determines the quality of the immune response to vaccination

The pre-exposure SARS-CoV-2-specific T cell repertoire determines the quality of the immune response to vaccination

Large-Scale Structure-Based Screening of Potential T Cell Cross-Reactivities Involving Peptide-Targets From BCG Vaccine and SARS-CoV-2

Distinct and dynamic activation profiles of circulating dendritic cells and monocytes in mild COVID‐19 and after yellow fever vaccination

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