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Vaccines
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T Cell Responses in SARS-CoV-2
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T Cell Responses in SARS-CoV-2

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "COVID-19 Vaccines and Vaccination".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 18448

Special Issue Editors

Dr. Kilian Schober

E-Mail Website
Guest Editor
Mikrobiologisches Institut – Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich- Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
Interests: T-cell immunology; SARS-CoV-2
Dr. Lucie Loyal

E-Mail Website1 Website2
Guest Editor
1. Si-M / “Der Simulierte Mensch” a Science Framework of Technische Universität Berlin and Charité - Universitätsmedizin Berlin, Berlin, Germany
2. Berlin Institute of Health at Charité, Universitätsmedizin Berlin, BIH Center for Regenerative Therapies, Berlin (BCRT), Germany
Interests: T-cell immunology; SARS-CoV-2

Special Issue Information

Dear Colleagues,

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is affecting the world’s population in manifold ways, and we are still searching for solutions in order to reach the stage of controlled endemicity. So far, research and vaccine development has largely focused on spike glycoprotein-specific antibody induction and stability, which is critical to avoid infection and limit the spread of SARS-CoV-2. However, increasing global immunity driving the evolution of escape mutations is increasing the importance of a broad, robust T-cell memory-based immunity. The development of second-generation vaccines will require an extensive knowledge of T-cell responses, including type and conservation of T-cell epitopes, pre-existing immunity as well as induction, compartmentalization, stability, and phenotype of overall T cell responses.

We would like to invite you to contribute to this Special Issue by submitting an original report, an original observation or a review that I) characterizes T-cell phenotypes and specificities in SARS-CoV-2 infection and vaccination, also considering existing and potential escape mutations, II) identifies correlates of T cell based protection in SARS-CoV-2 immunity, III) supports a better understanding of compartmentalization/infection and vaccination routes in the induction and stability of SARS-CoV-2 immunity and IV) contributes to the conceptualization and development of T-cell based vaccines.

Dr. Kilian Schober
Dr. Lucie Loyal
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • SARS-CoV-2
  • T cells
  • immune evasion
  • vaccines
  • cross-reactivity

Published Papers (7 papers)

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Research

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21 pages, 8194 KiB  
Article
Proinflammatory Innate Cytokines and Distinct Metabolomic Signatures Shape the T Cell Response in Active COVID-19
by Akshay Binayke, Aymaan Zaheer, Jyotsna Dandotiya, Sonu Kumar Gupta, Shailendra Mani, Manas Ranjan Tripathy, Upasna Madan, Tripti Shrivastava, Yashwant Kumar, Anil Kumar Pandey, Deepak Kumar Rathore and Amit Awasthi
Vaccines 2022, 10(10), 1762; https://doi.org/10.3390/vaccines10101762 - 20 Oct 2022
Cited by 7 | Viewed by 2801
Abstract
The underlying factors contributing to the evolution of SARS-CoV-2-specific T cell responses during COVID-19 infection remain unidentified. To address this, we characterized innate and adaptive immune responses with metabolomic profiling longitudinally at three different time points (0–3, 7–9, and 14–16 days post-COVID-19 positivity) [...] Read more.
The underlying factors contributing to the evolution of SARS-CoV-2-specific T cell responses during COVID-19 infection remain unidentified. To address this, we characterized innate and adaptive immune responses with metabolomic profiling longitudinally at three different time points (0–3, 7–9, and 14–16 days post-COVID-19 positivity) from young, mildly symptomatic, active COVID-19 patients infected during the first wave in mid-2020. We observed that anti-RBD IgG and viral neutralization are significantly reduced against the delta variant, compared to the ancestral strain. In contrast, compared to the ancestral strain, T cell responses remain preserved against the delta and omicron variants. We determined innate immune responses during the early stage of active infection, in response to TLR 3/7/8-mediated activation in PBMCs and serum metabolomic profiling. Correlation analysis indicated PBMCs-derived proinflammatory cytokines, IL-18, IL-1β, and IL-23, and the abundance of plasma metabolites involved in arginine biosynthesis were predictive of a robust SARS-CoV-2-specific Th1 response at a later stage (two weeks after PCR positivity). These observations may contribute to designing effective vaccines and adjuvants that promote innate immune responses and metabolites to induce a long-lasting anti-SARS-CoV-2-specific T cell response. Full article
(This article belongs to the Special Issue T Cell Responses in SARS-CoV-2)
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16 pages, 1957 KiB  
Article
Gene Signatures of T-Cell Activation Can Serve as Predictors of Functionality for SARS-CoV-2-Specific T-Cell Receptors
by Laura M. Mateyka, Philipp M. Strobl, Sebastian Jarosch, Sebastian J. C. Scheu, Dirk H. Busch and Elvira D’Ippolito
Vaccines 2022, 10(10), 1617; https://doi.org/10.3390/vaccines10101617 - 27 Sep 2022
Cited by 1 | Viewed by 2475
Abstract
The importance of T cells in controlling SARS-CoV-2 infections has been demonstrated widely, but insights into the quality of these responses are still limited due to technical challenges. Indeed, understanding the functionality of the T-cell receptor (TCR) repertoire of a polyclonal antigen-specific population [...] Read more.
The importance of T cells in controlling SARS-CoV-2 infections has been demonstrated widely, but insights into the quality of these responses are still limited due to technical challenges. Indeed, understanding the functionality of the T-cell receptor (TCR) repertoire of a polyclonal antigen-specific population still requires the tedious work of T-cell cloning or TCR re-expression and subsequent characterization. In this work, we show that it is possible to discriminate highly functional and bystander TCRs based on gene signatures of T-cell activation induced by recent peptide stimulation. SARS-CoV-2-specific TCRs previously identified by cytokine release after peptide restimulation and subsequent single-cell RNA sequencing were re-expressed via CRISPR-Cas9-mediated gene editing into a Jurkat-based reporter cell line system suitable for high-throughput screening. We could observe differences in SARS-CoV-2 epitope recognition as well as a wide range of functional avidities. By correlating these in vitro TCR engineered functional data with the transcriptomic profiles of the corresponding TCR-expressing parental T cells, we could validate that gene signatures of recent T-cell activation accurately identify and predict truly SARS-CoV-2-specific TCRs. In summary, this work paves the way for alternative approaches useful for the functional analysis of global antigen-specific TCR repertoires with largely improved throughput. Full article
(This article belongs to the Special Issue T Cell Responses in SARS-CoV-2)
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14 pages, 2312 KiB  
Article
Vaccine-Induced T-Cell and Antibody Responses at 12 Months after Full Vaccination Differ with Respect to Omicron Recognition
by Franz Mai, Johann Volzke, Emil C. Reisinger and Brigitte Müller-Hilke
Vaccines 2022, 10(9), 1563; https://doi.org/10.3390/vaccines10091563 - 19 Sep 2022
Cited by 4 | Viewed by 4305
Abstract
More than a year after the first vaccines against the novel SARS-CoV-2 were approved, many questions still remain about the long-term protection conferred by each vaccine. How long the effect lasts, how effective it is against variants of concern and whether further vaccinations [...] Read more.
More than a year after the first vaccines against the novel SARS-CoV-2 were approved, many questions still remain about the long-term protection conferred by each vaccine. How long the effect lasts, how effective it is against variants of concern and whether further vaccinations will confer additional benefits remain part of current and future research. For this purpose, we examined 182 health care employees—some of them with previous SARS-CoV-2 infection—12 months after different primary immunizations. To assess antibody responses, we performed an electrochemiluminescence assay (ECLIA) to determine anti-spike IgGs, followed by a surrogate virus neutralization assay against Wuhan-Hu-1 and B.1.1.529/BA.1 (Omicron). T cell response against wild-type and the Omicron variants of concern were assessed via interferon-gamma ELISpot assays and T-cell surface and intracellular cytokine staining. In summary, our results show that after the third vaccination with an mRNA vaccine, differences in antibody quantity and functionality observed after different primary immunizations were equalized. As for the T cell response, we were able to demonstrate a memory function for CD4+ and CD8+ T cells alike. Importantly, both T and antibody responses against wild-type and omicron differed significantly; however, antibody and T cell responses did not correlate with each other and, thus, may contribute differentially to immunity. Full article
(This article belongs to the Special Issue T Cell Responses in SARS-CoV-2)
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15 pages, 2334 KiB  
Article
Cellular and Humoral Immunity against Different SARS-CoV-2 Variants Is Detectable but Reduced in Vaccinated Kidney Transplant Patients
by Laura Thümmler, Anja Gäckler, Maren Bormann, Sandra Ciesek, Marek Widera, Hana Rohn, Neslinur Fisenkci, Mona Otte, Mira Alt, Ulf Dittmer, Peter A. Horn, Oliver Witzke, Adalbert Krawczyk and Monika Lindemann
Vaccines 2022, 10(8), 1348; https://doi.org/10.3390/vaccines10081348 - 18 Aug 2022
Cited by 7 | Viewed by 1693
Abstract
In kidney transplant (KTX) patients, immune responses after booster vaccination against SARS-CoV-2 are inadequately examined. We analyzed these patients a median of four months after a third/fourth vaccination and compared them to healthy controls. Cellular responses were analyzed by interferon-gamma (IFN-γ) and interleukin-2 [...] Read more.
In kidney transplant (KTX) patients, immune responses after booster vaccination against SARS-CoV-2 are inadequately examined. We analyzed these patients a median of four months after a third/fourth vaccination and compared them to healthy controls. Cellular responses were analyzed by interferon-gamma (IFN-γ) and interleukin-2 (IL-2) ELISpot assays. Neutralizing antibody titers were assessed against SARS-CoV-2 D614G (wild type) and the variants alpha, delta, and omicron by a cell culture-based neutralization assay. Humoral immunity was also determined by a competitive fluorescence assay, using 11 different variants of SARS-CoV-2. Antibody ratios were measured by ELISA. KTX patients showed significantly lower SARS-CoV-2-specific IFN-γ responses after booster vaccination than healthy controls. However, SARS-CoV-2-specific IL-2 responses were comparable to the T cell responses of healthy controls. Cell culture-based neutralizing antibody titers were 1.3-fold higher in healthy controls for D614G, alpha, and delta, and 7.8-fold higher for omicron (p < 0.01). Healthy controls had approximately 2-fold higher concentrations of potential neutralizing antibodies against all 11 variants than KTX patients. However, more than 60% of the KTX patients displayed antibodies to variants of SARS-CoV-2. Thus, KTX patients should be partly protected, due to neutralizing antibodies to variants of SARS-CoV-2 or by cross-reactive T cells, especially those producing IL-2. Full article
(This article belongs to the Special Issue T Cell Responses in SARS-CoV-2)
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14 pages, 2364 KiB  
Article
Cellular and Humoral Immunity after the Third Vaccination against SARS-CoV-2 in Hematopoietic Stem-Cell Transplant Recipients
by Laura Thümmler, Michael Koldehoff, Neslinur Fisenkci, Leonie Brochhagen, Peter A. Horn, Adalbert Krawczyk and Monika Lindemann
Vaccines 2022, 10(6), 972; https://doi.org/10.3390/vaccines10060972 - 18 Jun 2022
Cited by 3 | Viewed by 1964
Abstract
Protecting vulnerable groups from severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is mandatory. Immune responses after a third vaccination against SARS-CoV-2 are insufficiently studied in patients after hematopoietic stem-cell transplantation (HSCT). We analyzed immune responses before and after a third vaccination [...] Read more.
Protecting vulnerable groups from severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection is mandatory. Immune responses after a third vaccination against SARS-CoV-2 are insufficiently studied in patients after hematopoietic stem-cell transplantation (HSCT). We analyzed immune responses before and after a third vaccination in HSCT patients and healthy controls. Cellular immunity was assessed using interferon-gamma (IFN-γ) and interleukin-2 (IL-2) ELISpots. Furthermore, this is the first report on neutralizing antibodies against 11 variants of SARS-CoV-2, analyzed by competitive fluorescence assay. Humoral immunity was also measured by neutralization tests assessing cytopathic effects and by ELISA. Neither HSCT patients nor healthy controls displayed significantly higher SARS-CoV-2-specific IFN-γ or IL-2 responses after the third vaccination. However, after the third vaccination, cellular responses were 2.6-fold higher for IFN-γ and 3.2-fold higher for IL-2 in healthy subjects compared with HSCT patients. After the third vaccination, neutralizing antibodies were significantly higher (p < 0.01) in healthy controls, but not in HSCT patients. Healthy controls vs. HSCT patients had 1.5-fold higher concentrations of neutralizing antibodies against variants and 1.2-fold higher antibody concentrations against wildtype. However, half of the HSCT patients exhibited neutralizing antibodies to variants of SARS-CoV-2, which increased only slightly after a third vaccination. Full article
(This article belongs to the Special Issue T Cell Responses in SARS-CoV-2)
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Review

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12 pages, 810 KiB  
Review
Characteristics and Roles of T Follicular Helper Cells in SARS-CoV-2 Vaccine Response
by Xuyang Chi, Jia Gu and Xiaoxue Ma
Vaccines 2022, 10(10), 1623; https://doi.org/10.3390/vaccines10101623 - 28 Sep 2022
Cited by 2 | Viewed by 2327
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is critical to controlling the coronavirus disease 2019 (COVID-19) pandemic. However, a weak response to the vaccine and insufficient persistence of specific antibodies may threaten the global impact of mass vaccination campaigns. This study summarizes [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is critical to controlling the coronavirus disease 2019 (COVID-19) pandemic. However, a weak response to the vaccine and insufficient persistence of specific antibodies may threaten the global impact of mass vaccination campaigns. This study summarizes the internal factors of the body that affect the effectiveness of the SARS-CoV-2 vaccine. T follicular helper (Tfh) cells support germinal center B cells to produce vaccine-specific immunoglobulins. A reduction in the Tfh cell number and a shift in the subset phenotypes caused by multiple factors may impair the production and persistence of high-affinity antibodies. Besides efficacy differences caused by the different types of vaccines, the factors that affect vaccine effectiveness by intervening in the Tfh cell response also include age-related defects, the polarity of the body microenvironment, repeated immunization, immunodeficiency, and immunosuppressive treatments. Assessing the phenotypic distribution and activation levels of Tfh cell subsets after vaccination is helpful in predicting vaccine responses and may identify potential targets for improving vaccine effectiveness. Full article
(This article belongs to the Special Issue T Cell Responses in SARS-CoV-2)
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Other

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14 pages, 1529 KiB  
Brief Report
In Vitro Stimulation with Live SARS-CoV-2 Suggests Th17 Dominance In Virus-Specific CD4+ T Cell Response after COVID-19
by Igor Kudryavtsev, Victoria Matyushenko, Ekaterina Stepanova, Kirill Vasilyev, Larisa Rudenko and Irina Isakova-Sivak
Vaccines 2022, 10(9), 1544; https://doi.org/10.3390/vaccines10091544 - 16 Sep 2022
Viewed by 1831
Abstract
The SARS-CoV-2 and influenza viruses are the main causes of human respiratory tract infections with similar disease manifestation but distinct mechanisms of immunopathology and host response to the infection. In this study, we investigated the SARS-CoV-2-specific CD4+ T cell phenotype in comparison with [...] Read more.
The SARS-CoV-2 and influenza viruses are the main causes of human respiratory tract infections with similar disease manifestation but distinct mechanisms of immunopathology and host response to the infection. In this study, we investigated the SARS-CoV-2-specific CD4+ T cell phenotype in comparison with H1N1 influenza-specific CD4+ T cells. We determined the levels of SARS-CoV-2- and H1N1-specific CD4+ T cell responses in subjects recovered from COVID-19 one to 15 months ago by stimulating PBMCs with live SARS-CoV-2 or H1N1 influenza viruses. We investigated phenotypes and frequencies of main CD4+ T cell subsets specific for SARS-CoV-2 using an activation induced cell marker assay and multicolor flow cytometry, and compared the magnitude of SARS-CoV-2- and H1N1-specific CD4+ T cells. SARS-CoV-2-specific CD4+ T cells were detected 1–15 months post infection and the frequency of SARS-CoV-2-specific central memory CD4+ T cells was increased with the time post-symptom onset. Next, SARS-CoV-2-specific CD4+ T cells predominantly expressed the Th17 phenotype, but the level of Th17 cells in this group was lower than in H1N1-specific CD4+ T cells. Finally, we found that the lower level of total Th17 subset within total SARS-CoV-2-specific CD4+ T cells was linked with the low level of CCR4+CXCR3– ‘classical’ Th17 cells if compared with H1N1-specific Th17 cells. Taken together, our data suggest the involvement of Th17 cells and their separate subsets in the pathogenesis of SARS-CoV-2- and influenza-induced pneumonia; and a better understanding of Th17 mediated antiviral immune responses may lead to the development of new therapeutic strategies. Full article
(This article belongs to the Special Issue T Cell Responses in SARS-CoV-2)
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