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Book ; Online ; Thesis: An immunoinformatics approach for identification and characterization of T cell-mediated heterologous immunity between RNA viruses and allergens

Balz, Kathrin Jana [Verfasser] / Skevaki, Chrysanthi [Akademischer Betreuer]

2023

Author's details	Kathrin Jana Balz ; Betreuer: Chrysanthi Skevaki
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	German
Publisher	Philipps-Universität Marburg
Publishing place	Marburg
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: A novel mass cytometry protocol optimized for immunophenotyping of low-frequency antigen-specific T cells.

Balz, Kathrin / Grange, Magali / Pegel, Uta / Karamya, Zain A / Mello, Marielle / Zhou, Xiaoying / Berger, Thilo / Bloch, Konstantin / Dunham, Diane / Chinthrajah, Sharon / Nadeau, Kari / Luche, Hervé / Skevaki, Chrysanthi

Frontiers in cellular and infection microbiology

2024 Volume 13, Page(s) 1336489

Abstract: Understanding antigen-specific T-cell responses, for example, following virus infections or allergen exposure, is of high relevance for the development of vaccines and therapeutics. We aimed on optimizing immunophenotyping of T cells after antigen ... ...

Abstract	Understanding antigen-specific T-cell responses, for example, following virus infections or allergen exposure, is of high relevance for the development of vaccines and therapeutics. We aimed on optimizing immunophenotyping of T cells after antigen stimulation by improving staining procedures for flow and mass cytometry. Our method can be used for primary cells of both mouse and human origin for the detection of low-frequency T-cell response using a dual-barcoding system for individual samples and conditions. First, live-cell barcoding was performed using anti-CD45 antibodies prior to an
MeSH term(s)	Humans ; Animals ; Mice ; Flow Cytometry/methods ; Immunophenotyping ; Antigens ; T-Lymphocytes ; Staining and Labeling ; CD8-Positive T-Lymphocytes
Chemical Substances	Antigens
Language	English
Publishing date	2024-01-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2023.1336489
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Cross-reactive MHC class I T cell epitopes may dictate heterologous immune responses between respiratory viruses and food allergens.

Balz, Kathrin / Kaushik, Abhinav / Cemic, Franz / Sampath, Vanitha / Heger, Vanessa / Renz, Harald / Nadeau, Kari / Skevaki, Chrysanthi

Scientific reports

2023 Volume 13, Issue 1, Page(s) 14874

Abstract: Respiratory virus infections play a major role in asthma, while there is a close correlation between asthma and food allergy. We hypothesized that T cell-mediated heterologous immunity may induce asthma symptoms among sensitized individuals and used two ... ...

Abstract	Respiratory virus infections play a major role in asthma, while there is a close correlation between asthma and food allergy. We hypothesized that T cell-mediated heterologous immunity may induce asthma symptoms among sensitized individuals and used two independent in silico pipelines for the identification of cross-reactive virus- and food allergen- derived T cell epitopes, considering individual peptide sequence similarity, MHC binding affinity and immunogenicity. We assessed the proteomes of human rhinovirus (RV1b), respiratory syncytial virus (RSVA2) and influenza-strains contained in the seasonal quadrivalent influenza vaccine 2019/2020 (QIV 2019/2020), as well as SARS-CoV-2 for human HLA alleles, in addition to more than 200 most common food allergen protein sequences. All resulting allergen-derived peptide candidates were subjected to an elaborate scoring system considering multiple criteria, including clinical relevance. In both bioinformatics approaches, we found that shortlisted peptide pairs that are potentially binding to MHC class II molecules scored up to 10 × lower compared to MHC class I candidate epitopes. For MHC class I food allergen epitopes, several potentially cross-reactive peptides from shrimp, kiwi, apple, soybean and chicken were identified. The shortlisted set of peptide pairs may be implicated in heterologous immune responses and translated to peptide immunization strategies with immunomodulatory properties.
MeSH term(s)	Humans ; Epitopes, T-Lymphocyte ; COVID-19 ; SARS-CoV-2 ; Asthma ; Food Hypersensitivity
Chemical Substances	Epitopes, T-Lymphocyte
Language	English
Publishing date	2023-09-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-41187-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A broadly protective vaccine against cutaneous human papillomaviruses.

Mariz, Filipe Colaco / Balz, Kathrin / Dittrich, Manuela / Zhang, Yueru / Yang, Fan / Zhao, Xueer / Bolchi, Angelo / Ottonello, Simone / Müller, Martin

NPJ vaccines

2022 Volume 7, Issue 1, Page(s) 116

Abstract: Skin colonization by human papillomavirus (HPV) is typically related to inconspicuous cutaneous infections without major disease or complications in immunocompetent individuals. However, in immunosuppressed patients, especially organ transplanted ... ...

Abstract	Skin colonization by human papillomavirus (HPV) is typically related to inconspicuous cutaneous infections without major disease or complications in immunocompetent individuals. However, in immunosuppressed patients, especially organ transplanted recipients, cutaneous HPV infections may cause massive, highly spreading and recurrent skin lesions upon synergism with UV-exposure. Current HPV prophylactic vaccines are not effective against cutaneous HPV types (cHPV). By applying a modular polytope-based approach, in this work, we explored different vaccine candidates based on selected, tandemly arranged cHPV-L2 epitopes fused to thioredoxin (Trx) as a scaffold protein. Upon conversion to heptameric nanoparticles with the use of a genetically fused oligomerization domain, our candidate Trx-L2 vaccines induce broadly neutralizing immune responses against 19 cHPV in guinea pigs. Similar findings were obtained in mice, where protection against virus challenge was also achieved via passive transfer of immune sera. Remarkably, immunization with the candidate cHPV vaccines also induced immune responses against several mucosal low- and high-risk HPV types, including HPV16 and 18. Based on cumulative immunogenicity data but also on ease and yield of production, we identified a lead vaccine candidate bearing 12 different cHPV-L2 epitopes that holds great promise as a scalable and GMP production-compatible lead molecule for the prevention of post-transplantation skin lesions caused by cHPV infection.
Language	English
Publishing date	2022-10-10
Publishing country	England
Document type	Journal Article
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-022-00539-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Virus-Induced T Cell-Mediated Heterologous Immunity and Vaccine Development.

Balz, Kathrin / Trassl, Lilith / Härtel, Valerie / Nelson, Philipp P / Skevaki, Chrysanthi

Frontiers in immunology

2020 Volume 11, Page(s) 513

Abstract: Heterologous immunity (H.I.) is a consequence of an encounter with a specific antigen, which can alter the subsequent immune response to a different antigen. This can happen at the innate immune system level-often called trained immunity or innate immune ...

Abstract	Heterologous immunity (H.I.) is a consequence of an encounter with a specific antigen, which can alter the subsequent immune response to a different antigen. This can happen at the innate immune system level-often called trained immunity or innate immune memory-and/or at the adaptive immune system level involving T memory cells and antibodies. Viruses may also induce T cell-mediated H.I., which can confer protection or drive immunopathology against other virus subtypes, related or unrelated viruses, other pathogens, auto- or allo-antigens. It is important to understand the underlying mechanisms for the development of antiviral "universal" vaccines and broader T cell responses rather than just subtype-specific antibody responses as in the case of influenza. Furthermore, knowledge about determinants of vaccine-mediated H.I. may inform public health policies and provide suggestions for repurposing existing vaccines. Here, we introduce H.I. and provide an overview of evidence on virus- and antiviral vaccine-induced T cell-mediated cross-reactive responses. We also discuss the factors influencing final clinical outcome of virus-mediated H.I. as well as non-specific beneficial effects of live attenuated antiviral vaccines such as measles and vaccinia. Available epidemiological and mechanistic data have implications both for the development of new vaccines and for personalized vaccinology, which are presented. Finally, we formulate future research priorities and opportunities.
MeSH term(s)	Animals ; Cross Reactions/immunology ; Humans ; Immunity, Cellular/immunology ; Immunity, Heterologous/immunology ; T-Lymphocytes/immunology ; Viral Vaccines/immunology ; Virus Diseases/immunology
Chemical Substances	Viral Vaccines
Keywords	covid19
Language	English
Publishing date	2020-03-31
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.00513
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Homologies between SARS-CoV-2 and allergen proteins may direct T cell-mediated heterologous immune responses.

Balz, Kathrin / Kaushik, Abhinav / Chen, Meng / Cemic, Franz / Heger, Vanessa / Renz, Harald / Nadeau, Kari / Skevaki, Chrysanthi

Scientific reports

2021 Volume 11, Issue 1, Page(s) 4792

Abstract: The outbreak of the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a public health emergency. Asthma does not represent a risk factor for COVID-19 in several published cohorts. We hypothesized that the SARS-CoV-2 proteome contains T ... ...

Abstract	The outbreak of the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a public health emergency. Asthma does not represent a risk factor for COVID-19 in several published cohorts. We hypothesized that the SARS-CoV-2 proteome contains T cell epitopes, which are potentially cross-reactive to allergen epitopes. We aimed at identifying homologous peptide sequences by means of two distinct complementary bioinformatics approaches. Pipeline 1 included prediction of MHC Class I and Class II epitopes contained in the SARS-CoV-2 proteome and allergens along with alignment and elaborate ranking approaches. Pipeline 2 involved alignment of SARS-CoV-2 overlapping peptides with known allergen-derived T cell epitopes. Our results indicate a large number of MHC Class I epitope pairs including known as well as de novo predicted allergen T cell epitopes with high probability for cross-reactivity. Allergen sources, such as Aspergillus fumigatus, Phleum pratense and Dermatophagoides species are of particular interest due to their association with multiple cross-reactive candidate peptides, independently of the applied bioinformatic approach. In contrast, peptides derived from food allergens, as well as MHC class II epitopes did not achieve high in silico ranking and were therefore not further investigated. Our findings warrant further experimental confirmation along with examination of the functional importance of such cross-reactive responses.
MeSH term(s)	Allergens/immunology ; Asthma/immunology ; COVID-19/immunology ; Computational Biology ; Epitopes, T-Lymphocyte/immunology ; HLA Antigens/immunology ; Humans ; Immunity, Cellular ; Immunity, Heterologous ; SARS-CoV-2/immunology ; T-Lymphocytes/immunology ; Viral Proteins/immunology
Chemical Substances	Allergens ; Epitopes, T-Lymphocyte ; HLA Antigens ; Viral Proteins
Language	English
Publishing date	2021-02-26
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-84320-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Homologies between SARS-CoV-2 and allergen proteins may direct T cell-mediated heterologous immune responses.

Balz, Kathrin / Chen, Meng / Kaushik, Abhinav / Cemic, Franz / Heger, Vanessa / Renz, Harald / Nadeau, Kari / Skevaki, Chrysanthi

Research square

2020

Abstract: The outbreak of the new Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a public health emergency. Asthma does not represent a risk factor for COVID-19 in several published cohorts. We hypothesized that the SARS-CoV-2 proteome contains T ... ...

Abstract	The outbreak of the new Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a public health emergency. Asthma does not represent a risk factor for COVID-19 in several published cohorts. We hypothesized that the SARS-CoV-2 proteome contains T cell epitopes, which are potentially cross-reactive to allergen epitopes. We aimed at identifying homologous peptide sequences by means of two distinct complementary bioinformatics approaches. Pipeline 1 included prediction of MHC Class I and Class II epitopes contained in the SARS-CoV-2 proteome and allergens along with alignment and elaborate ranking approaches. Pipeline 2 involved alignment of SARS-CoV-2 overlapping peptides with known allergen-derived T cell epitopes. Our results indicate a large number of MHC Class I epitope pairs including known as well as
Keywords	covid19
Language	English
Publishing date	2020-10-06
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-86873/v1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Homologies between SARS-CoV-2 and allergen proteins may direct T cell-mediated heterologous immune responses

Kathrin Balz / Abhinav Kaushik / Meng Chen / Franz Cemic / Vanessa Heger / Harald Renz / Kari Nadeau / Chrysanthi Skevaki

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 7

Abstract: Abstract The outbreak of the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a public health emergency. Asthma does not represent a risk factor for COVID-19 in several published cohorts. We hypothesized that the SARS-CoV-2 proteome ... ...

Abstract	Abstract The outbreak of the new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a public health emergency. Asthma does not represent a risk factor for COVID-19 in several published cohorts. We hypothesized that the SARS-CoV-2 proteome contains T cell epitopes, which are potentially cross-reactive to allergen epitopes. We aimed at identifying homologous peptide sequences by means of two distinct complementary bioinformatics approaches. Pipeline 1 included prediction of MHC Class I and Class II epitopes contained in the SARS-CoV-2 proteome and allergens along with alignment and elaborate ranking approaches. Pipeline 2 involved alignment of SARS-CoV-2 overlapping peptides with known allergen-derived T cell epitopes. Our results indicate a large number of MHC Class I epitope pairs including known as well as de novo predicted allergen T cell epitopes with high probability for cross-reactivity. Allergen sources, such as Aspergillus fumigatus, Phleum pratense and Dermatophagoides species are of particular interest due to their association with multiple cross-reactive candidate peptides, independently of the applied bioinformatic approach. In contrast, peptides derived from food allergens, as well as MHC class II epitopes did not achieve high in silico ranking and were therefore not further investigated. Our findings warrant further experimental confirmation along with examination of the functional importance of such cross-reactive responses.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Homologies between SARS-CoV-2 and allergen proteins may direct T cell-mediated heterologous immune responses

Balz, Kathrin / Chen, Meng / Kaushik, Abhinav / Cemic, Franz / Heger, Vanessa / Renz, Harald / Nadeau, Kari / Skevaki, Chrysanthi

Abstract	The outbreak of the new Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a public health emergency. Asthma does not represent a risk factor for COVID-19 in several published cohorts. We hypothesized that the SARS-CoV-2 proteome contains T cell epitopes, which are potentially cross-reactive to allergen epitopes. We aimed at identifying homologous peptide sequences by means of two distinct complementary bioinformatics approaches. Pipeline 1 included prediction of MHC Class I and Class II epitopes contained in the SARS-CoV-2 proteome and allergens along with alignment and elaborate ranking approaches. Pipeline 2 involved alignment of SARS-CoV-2 overlapping peptides with known allergen-derived T cell epitopes. Our results indicate a large number of MHC Class I epitope pairs including known as well as de novo predicted allergen T cell epitopes with high probability for cross-reactivity. Allergen sources, such as Aspergillus fumigatus , Phleum pratense and Dermatophagoides species are of particular interest due to their association with multiple cross-reactive candidate peptides, independently of the applied bioinformatic approach. In contrast, peptides derived from food allergens, as well as MHC class II epitopes did not achieve high in silico ranking and were therefore not further investigated. Our findings warrant further experimental confirmation along with examination of the functional importance of such cross-reactive responses.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #869427
Database	COVID19

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Article ; Online: Correction to: Informed consent and informed intervention: SARS‑CoV‑2 vaccinations not just call for disclosure of newly emerging safety data but also for hypothesis generation and testing.

Fischer, Johannes C / Schmidt, Albrecht G / Bölke, Edwin / Keitel, Verena / Feldt, Torsten / Jensen, Björn / Freise, Noemi F / Häussinger, Dieter / Schneider, E Marion / Hermsen, Derik / Kindgen-Milles, Detlef / Knoefel, Wolfram Trudo / Haussmann, Jan / Tamaskovics, Balint / Plettenberg, Christian / Scheckenbach, Kathrin / Corradini, Stefanie / Rox, Jutta / Balz, Vera /

Maas, Kitti / Schmidt, Livia / Grebe, Olaf / Ehrhardt, Anja / Gerber, Peter Arne / Peiper, Matthias / Buhren, Bettina Alexandra / Lichtenberg, Artur / Rezazadeh, Amir / Budach, Wilfried / Matuschek, Christiane

European journal of medical research

2021 Volume 26, Issue 1, Page(s) 104

Language	English
Publishing date	2021-09-13
Publishing country	England
Document type	Published Erratum
ZDB-ID	1329381-3
ISSN	2047-783X ; 0949-2321
ISSN (online)	2047-783X
ISSN	0949-2321
DOI	10.1186/s40001-021-00574-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

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