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Article ; Online: Single-epitope T cell-based vaccine protects against SARS-CoV-2 infection in a preclinical animal model.

Tada, Takuya / Peng, Ju-Yi / Dcosta, Belinda M / Landau, Nathaniel R

JCI insight

2023 Volume 8, Issue 7

Abstract: Currently authorized COVID-19 vaccines induce humoral and cellular responses to epitopes in the SARS-CoV-2 spike protein, though the relative roles of antibodies and T cells in protection are not well understood. To understand the role of vaccine- ... ...

Abstract	Currently authorized COVID-19 vaccines induce humoral and cellular responses to epitopes in the SARS-CoV-2 spike protein, though the relative roles of antibodies and T cells in protection are not well understood. To understand the role of vaccine-elicited T cell responses in protection, we established a T cell-only vaccine using a DC-targeted lentiviral vector expressing single CD8+ T cell epitopes of the viral nucleocapsid, spike, and ORF1. Immunization of angiotensin-converting enzyme 2-transgenic mice with ex vivo lentiviral vector-transduced DCs or by direct injection of the vector induced the proliferation of functional antigen-specific CD8+ T cells, resulting in a 3-log decrease in virus load upon live virus challenge that was effective against the ancestral virus and Omicron variants. The Pfizer/BNT162b2 vaccine was also protective in mice, but the antibodies elicited did not cross-react on the Omicron variants, suggesting that the protection was mediated by T cells. The studies suggest that the T cell response plays an important role in vaccine protection. The findings suggest that the incorporation of additional T cell epitopes into current vaccines would increase their effectiveness and broaden protection.
MeSH term(s)	Animals ; Humans ; Mice ; COVID-19/prevention & control ; COVID-19 Vaccines ; Epitopes, T-Lymphocyte ; BNT162 Vaccine ; SARS-CoV-2 ; Vaccines ; Antibodies ; Mice, Transgenic ; Models, Animal
Chemical Substances	spike protein, SARS-CoV-2 ; COVID-19 Vaccines ; Epitopes, T-Lymphocyte ; BNT162 Vaccine ; Vaccines ; Antibodies
Language	English
Publishing date	2023-04-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.167306
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Single-epitope T cell–based vaccine protects against SARS-CoV-2 infection in a preclinical animal model

Takuya Tada / Ju-Yi Peng / Belinda M. Dcosta / Nathaniel R. Landau

JCI Insight, Vol 8, Iss

2023 Volume 7

Abstract	Currently authorized COVID-19 vaccines induce humoral and cellular responses to epitopes in the SARS-CoV-2 spike protein, though the relative roles of antibodies and T cells in protection are not well understood. To understand the role of vaccine-elicited T cell responses in protection, we established a T cell–only vaccine using a DC-targeted lentiviral vector expressing single CD8+ T cell epitopes of the viral nucleocapsid, spike, and ORF1. Immunization of angiotensin-converting enzyme 2–transgenic mice with ex vivo lentiviral vector–transduced DCs or by direct injection of the vector induced the proliferation of functional antigen-specific CD8+ T cells, resulting in a 3-log decrease in virus load upon live virus challenge that was effective against the ancestral virus and Omicron variants. The Pfizer/BNT162b2 vaccine was also protective in mice, but the antibodies elicited did not cross-react on the Omicron variants, suggesting that the protection was mediated by T cells. The studies suggest that the T cell response plays an important role in vaccine protection. The findings suggest that the incorporation of additional T cell epitopes into current vaccines would increase their effectiveness and broaden protection.
Keywords	COVID-19 ; Immunology ; Medicine ; R
Subject code	570
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	American Society for Clinical investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Time-dependent viral interference between influenza virus and coronavirus in the infection of differentiated porcine airway epithelial cells.

Peng, Ju-Yi / Shin, Dai-Lun / Li, Guangxing / Wu, Nai-Huei / Herrler, Georg

Virulence

2021 Volume 12, Issue 1, Page(s) 1111–1121

Abstract: Coronaviruses and influenza viruses are circulating in humans and animals all over the world. Co-infection with these two viruses may aggravate clinical signs. However, the molecular mechanisms of co-infections by these two viruses are incompletely ... ...

Abstract	Coronaviruses and influenza viruses are circulating in humans and animals all over the world. Co-infection with these two viruses may aggravate clinical signs. However, the molecular mechanisms of co-infections by these two viruses are incompletely understood. In this study, we applied air-liquid interface (ALI) cultures of well-differentiated porcine tracheal epithelial cells (PTECs) to analyze the co-infection by a swine influenza virus (SIV, H3N2 subtype) and porcine respiratory coronavirus (PRCoV) at different time intervals. Our results revealed that in short-term intervals, prior infection by influenza virus caused complete inhibition of coronavirus infection, while in long-term intervals, some coronavirus replication was detectable. The influenza virus infection resulted in (i) an upregulation of porcine aminopeptidase N, the cellular receptor for PRCoV and (ii) in the induction of an innate immune response which was responsible for the inhibition of PRCoV replication. By contrast, prior infection by coronavirus only caused a slight inhibition of influenza virus replication. Taken together, the timing and the order of virus infection are important determinants in co-infections. This study is the first to show the impact of SIV and PRCoV co- and super-infection on the cellular level. Our results have implications also for human viruses, including potential co-infections by SARS-CoV-2 and seasonal influenza viruses.
MeSH term(s)	Animals ; CD13 Antigens/metabolism ; Cells, Cultured ; Coinfection/virology ; Coronavirus Infections/virology ; Epithelial Cells/immunology ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; Epithelial Cells/virology ; Immunity, Innate ; Influenza A Virus, H3N2 Subtype/physiology ; Orthomyxoviridae Infections/virology ; Porcine Respiratory Coronavirus/physiology ; Swine ; Trachea/cytology ; Viral Interference ; Virus Replication
Chemical Substances	CD13 Antigens (EC 3.4.11.2)
Language	English
Publishing date	2021-06-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2657572-3
ISSN	2150-5608 ; 2150-5594
ISSN (online)	2150-5608
ISSN	2150-5594
DOI	10.1080/21505594.2021.1911148
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Book ; Online ; Thesis: The The interaction of respiratory pathogens with differentiated porcine and canine airway epithelial cells

Peng, Ju-Yi [Verfasser] / Herrler, Georg [Akademischer Betreuer] / Becher, Paul [Akademischer Betreuer] / Zimmer, Gert [Gutachter]

2021

Author's details	Ju-Yi Peng ; Gutachter: Gert Zimmer ; Georg Herrler, Paul Becher
Keywords	Landwirtschaft, Veterinärmedizin ; Agriculture, Veterinary Science
Subject code	sg630
Language	English
Publisher	Stiftung Tierärztliche Hochschule Hannover
Publishing place	Hannover
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: Overcoming the Barrier of the Respiratory Epithelium during Canine Distemper Virus Infection.

Shin, Dai-Lun / Chludzinski, Elisa / Wu, Nai-Huei / Peng, Ju-Yi / Ciurkiewicz, Malgorzata / Sawatsky, Bevan / Pfaller, Christian K / Baechlein, Christine / von Messling, Veronika / Haas, Ludwig / Beineke, Andreas / Herrler, Georg

mBio

2022 Volume 13, Issue 1, Page(s) e0304321

Abstract: Canine distemper virus (CDV) is a highly contagious pathogen and is known to enter the host via the respiratory tract and disseminate to various organs. Current hypotheses speculate that CDV uses the homologous cellular receptors of measles virus (MeV), ... ...

Abstract	Canine distemper virus (CDV) is a highly contagious pathogen and is known to enter the host via the respiratory tract and disseminate to various organs. Current hypotheses speculate that CDV uses the homologous cellular receptors of measles virus (MeV), SLAM and nectin-4, to initiate the infection process. For validation, here, we established the well-differentiated air-liquid interface (ALI) culture model from primary canine tracheal airway epithelial cells. By applying the green fluorescent protein (GFP)-expressing CDV vaccine strain and recombinant wild-type viruses, we show that cell-free virus infects the airway epithelium mainly via the paracellular route and only after prior disruption of tight junctions by pretreatment with EGTA; this infection was related to nectin-4 but not to SLAM. Remarkably, when CDV-preinfected DH82 cells were cocultured on the basolateral side of canine ALI cultures grown on filter supports with a 1.0-μm pore size, cell-associated CDV could be transmitted via cell-to-cell contact from immunocytes to airway epithelial cultures. Finally, we observed that canine ALI cultures formed syncytia and started to release cell-free infectious viral particles from the apical surface following treatment with an inhibitor of the JAK/STAT signaling pathway (ruxolitinib). Our findings show that CDV can overcome the epithelial barrier through different strategies, including infection via immunocyte-mediated transmission and direct infection via the paracellular route when tight junctions are disrupted. Our established model can be adapted to other animals for studying the transmission routes and the pathogenicity of other morbilliviruses.
MeSH term(s)	Animals ; Dogs ; Distemper Virus, Canine/metabolism ; Nectins ; Egtazic Acid ; Receptors, Cell Surface/metabolism ; Measles virus ; Cell Adhesion Molecules/metabolism ; Respiratory Mucosa/metabolism ; Distemper
Chemical Substances	Nectins ; Egtazic Acid (526U7A2651) ; Receptors, Cell Surface ; Cell Adhesion Molecules
Language	English
Publishing date	2022-01-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.03043-21
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Microstrain-Stimulated Elastico-Mechanoluminescence with Dual-Mode Stress Sensing.

Yang, Hang / Wei, Yi / Ju, Haonan / Huang, Xinru / Li, Jun / Wang, Wei / Peng, Dengfeng / Tu, Dong / Li, Guogang

Advanced materials (Deerfield Beach, Fla.)

2024 , Page(s) e2401296

Abstract: Elastico-mechanoluminescence technology has shown significant application prospects in stress sensing, artificial skin, remote interaction, and other research areas. Its progress mainly lies in realizing stress visualization and 2D or even 3D stress- ... ...

Abstract	Elastico-mechanoluminescence technology has shown significant application prospects in stress sensing, artificial skin, remote interaction, and other research areas. Its progress mainly lies in realizing stress visualization and 2D or even 3D stress-sensing effects using a passive sensing mode. However, the widespread promotion of mechanoluminescence (ML) technology is hindered by issues such as high stress or strain thresholds and a single sensing mode based on luminous intensity. In this study, a highly efficient green-emitting ML with dual-mode stress-sensing characteristics driven by microscale strain is developed using LiTaO
Language	English
Publishing date	2024-04-10
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1474949-X
ISSN	1521-4095 ; 0935-9648
ISSN (online)	1521-4095
ISSN	0935-9648
DOI	10.1002/adma.202401296
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Article: Corrigendum: Case report: Ruptured internal carotid artery fusiform aneurysm mimicking pituitary apoplexy after stereotactic radiosurgery.

Wang, Peng Wei / Chung, Ming Hsuan / Feng, Shao Wei / Liao, Hsiang Chih / Wu, Yi Chieh / Hueng, Dueng Yuan / Yang, Yun Ju / Ju, Da Tong

Frontiers in neurology

2023 Volume 14, Page(s) 1301436

Abstract: This corrects the article DOI: 10.3389/fneur.2023.1219372.]. ...

Abstract	[This corrects the article DOI: 10.3389/fneur.2023.1219372.].
Language	English
Publishing date	2023-10-10
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2023.1301436
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Article ; Online: The Cell Tropism of Porcine Respiratory Coronavirus for Airway Epithelial Cells Is Determined by the Expression of Porcine Aminopeptidase N.

Peng, Ju-Yi / Punyadarsaniya, Darsaniya / Shin, Dai-Lun / Pavasutthipaisit, Suvarin / Beineke, Andreas / Li, Guangxing / Wu, Nai-Huei / Herrler, Georg

Viruses

2020 Volume 12, Issue 11

Abstract: Porcine respiratory coronavirus (PRCoV) infects the epithelial cells in the respiratory tract of pigs, causing a mild respiratory disease. We applied air-liquid interface (ALI) cultures of well-differentiated porcine airway cells to mimic the respiratory ...

Abstract	Porcine respiratory coronavirus (PRCoV) infects the epithelial cells in the respiratory tract of pigs, causing a mild respiratory disease. We applied air-liquid interface (ALI) cultures of well-differentiated porcine airway cells to mimic the respiratory tract epithelium in vitro and use it for analyzing the infection by PRCoV. As reported for most coronaviruses, virus entry and virus release occurred mainly via the apical membrane domain. A novel finding was that PRCoV preferentially targets non-ciliated and among them the non-mucus-producing cells. Aminopeptidase N (APN), the cellular receptor for PRCoV was also more abundantly expressed on this type of cell suggesting that APN is a determinant of the cell tropism. Interestingly, differentiation-dependent differences were found both in the expression of pAPN and the susceptibility to PRCoV infection. Cells in an early differentiation stage express higher levels of pAPN and are more susceptible to infection by PRCoV than are well-differentiated cells. A difference in the susceptibility to infection was also detected when tracheal and bronchial cells were compared. The increased susceptibility to infection of bronchial epithelial cells was, however, not due to an increased abundance of APN on the cell surface. Our data reveal a complex pattern of infection in porcine differentiated airway epithelial cells that could not be elucidated with immortalized cell lines. The results are expected to have relevance also for the analysis of other respiratory viruses.
MeSH term(s)	Animals ; Bronchi/metabolism ; Bronchi/virology ; CD13 Antigens/metabolism ; Cell Differentiation ; Cells, Cultured ; Epithelial Cells/cytology ; Epithelial Cells/metabolism ; Epithelial Cells/virology ; Porcine Respiratory Coronavirus/physiology ; Receptors, Virus/metabolism ; Respiratory Mucosa/virology ; Swine ; Trachea/metabolism ; Trachea/virology ; Viral Tropism ; Virus Internalization ; Virus Release ; Virus Replication
Chemical Substances	Receptors, Virus ; CD13 Antigens (EC 3.4.11.2)
Keywords	covid19
Language	English
Publishing date	2020-10-23
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v12111211
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Article ; Online: A Portable Wireless Urine Detection System With Power-Efficient Electrochemical Readout ASIC and ABTS-CNT Biosensor for UACR Detection.

Lee, Shuenn-Yuh / Lee, Hao-Yun / Ciou, Ding-Siang / Liao, Zhan-Xian / Huang, Peng-Wei / Hsieh, Yi-Ting / Wei, Yi-Chieh / Lin, Chia-Yu / Shieh, Meng-Dar / Chen, Ju-Yi

IEEE transactions on biomedical circuits and systems

2021 Volume 15, Issue 3, Page(s) 537–548

Abstract: This work presents a portable wireless urine detection system which consists of an electrochemical readout application specific integrated circuit (ASIC) and a biosensor composed of 2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) and carbon ... ...

Abstract	This work presents a portable wireless urine detection system which consists of an electrochemical readout application specific integrated circuit (ASIC) and a biosensor composed of 2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) and carbon nanotube (ABTS-CNT) for the detection of urine albumin-to-creatinine ratio (UACR). The ASIC includes a potentiostat, a digital circuitry and a power management circuit which can perform electrochemistry techniques with a dual-channel screen-printing carbon electrode (SPCE). Electrochemical experiments on the proposed biosensor (SPCE\|ABTS-CNT\|Nafion) have revealed promising sensing characteristics for creatinine and human serum albumin detection. Practical urine tests has demonstrated the capability of the proposed urine detection system for UACR detection with both the power-efficient readout ASIC and the ABTS-CNT biosensor. A user-friendly prototype has also been designed which can be useful for either personal health administrationor homecare.
MeSH term(s)	Benzothiazoles ; Biosensing Techniques ; Electrochemical Techniques ; Electrochemistry ; Humans ; Nanotubes, Carbon ; Sulfonic Acids
Chemical Substances	Benzothiazoles ; Nanotubes, Carbon ; Sulfonic Acids ; 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid (28752-68-3)
Language	English
Publishing date	2021-08-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-9990
ISSN (online)	1940-9990
DOI	10.1109/TBCAS.2021.3087475
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Article ; Online: Avian Influenza A Virus Infects Swine Airway Epithelial Cells without Prior Adaptation.

Shin, Dai-Lun / Yang, Wei / Peng, Ju-Yi / Sawatsky, Bevan / von Messling, Veronika / Herrler, Georg / Wu, Nai-Huei

Viruses

2020 Volume 12, Issue 6

Abstract: Pigs play an important role in the interspecies transmission of influenza A viruses (IAV). The porcine airway epithelium contains binding sites for both swine/human IAV (α2,6-linked sialic acids) and avian IAV (α2,3-linked sialic acids) and therefore is ... ...

Abstract	Pigs play an important role in the interspecies transmission of influenza A viruses (IAV). The porcine airway epithelium contains binding sites for both swine/human IAV (α2,6-linked sialic acids) and avian IAV (α2,3-linked sialic acids) and therefore is suited for adaptation of viruses from other species as suggested by the "mixing vessel theory". Here, we applied well-differentiated swine airway epithelial cells to find out whether efficient infection by avian IAV requires prior adaption. Furthermore, we analyzed the influence of the sialic acid-binding activity and the virus-induced detrimental effects. Surprisingly, an avian IAV H1N1 strain circulating in European poultry and waterfowl shows increased and prolonged viral replication without inducing a strong innate immune response. This virus could infect the lower respiratory tract in our precision cut-lung slice model. Pretreating the cells with poly (I:C) and/or JAK/STAT pathway inhibitors revealed that the interferon-stimulated innate immune response influences the replication of avian IAV in swine airway epitheliums but not that of swine IAV. Further studies indicated that in the infection by IAVs, the binding affinity of sialic acid is not the sole factor affecting the virus infectivity for swine or human airway epithelial cells, whereas it may be crucial in well-differentiated ferret tracheal epithelial cells. Taken together, our results suggest that the role of pigs being the vessel of interspecies transmission should be reconsidered, and the potential of avian H1N1 viruses to infect mammals needs to be characterized in more detail.
MeSH term(s)	Animals ; Bronchi/cytology ; Bronchi/virology ; Cells, Cultured ; Fluorescent Antibody Technique ; Influenza A virus/pathogenicity ; Janus Kinase 2/metabolism ; Lung/virology ; Orthomyxoviridae Infections/veterinary ; Orthomyxoviridae Infections/virology ; Real-Time Polymerase Chain Reaction ; Respiratory Mucosa/virology ; STAT1 Transcription Factor/metabolism ; Signal Transduction ; Swine ; Swine Diseases/virology ; Trachea/cytology ; Trachea/virology
Chemical Substances	STAT1 Transcription Factor ; Janus Kinase 2 (EC 2.7.10.2)
Keywords	covid19
Language	English
Publishing date	2020-05-28
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v12060589
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