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  1. Article: Enhanced Ability of Oligomeric Nanobodies Targeting MERS Coronavirus Receptor-Binding Domain

    Tai, Wanbo

    Viruses, 11(2):166

    2019  

    Abstract: Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV), an infectious coronavirus first reported in 2012, has a mortality rate greater than 35%. Therapeutic antibodies are key tools for preventing and treating MERS-CoV infection, but to date no ... ...

    Abstract Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV), an infectious coronavirus first reported in 2012, has a mortality rate greater than 35%. Therapeutic antibodies are key tools for preventing and treating MERS-CoV infection, but to date no such agents have been approved for treatment of this virus. Nanobodies (Nbs) are camelid heavy chain variable domains with properties distinct from those of conventional antibodies and antibody fragments. We generated two oligomeric Nbs by linking two or three monomeric Nbs (Mono-Nbs) targeting the MERS-CoV receptor-binding domain (RBD), and compared their RBD-binding affinity, RBD–receptor binding inhibition, stability, and neutralizing and cross-neutralizing activity against MERS-CoV. Relative to Mono-Nb, dimeric Nb (Di-Nb) and trimeric Nb (Tri-Nb) had significantly greater ability to bind MERS-CoV RBD proteins with or without mutations in the RBD, thereby potently blocking RBD–MERS-CoV receptor binding. The engineered oligomeric Nbs were very stable under extreme conditions, including low or high pH, protease (pepsin), chaotropic denaturant (urea), and high temperature. Importantly, Di-Nb and Tri-Nb exerted significantly elevated broad-spectrum neutralizing activity against at least 19 human and camel MERS-CoV strains isolated in different countries and years. Overall, the engineered Nbs could be developed into effective therapeutic agents for prevention and treatment of MERS-CoV infection.
    Keywords COVID-19 ; Coronavirus ; MERS-CoV ; cross-neutralization ; nanobodies ; receptor-binding domain ; therapeutic antibodies
    Language English
    Document type Article
    Database Repository for Life Sciences

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  2. Article ; Online: T-cell immunity: a barrier to Omicron immune evasion.

    Yu, Fei / Tai, Wanbo / Cheng, Gong

    Signal transduction and targeted therapy

    2022  Volume 7, Issue 1, Page(s) 297

    MeSH term(s) Immune Evasion ; T-Lymphocytes
    Language English
    Publishing date 2022-08-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 2886872-9
    ISSN 2059-3635 ; 2095-9907
    ISSN (online) 2059-3635
    ISSN 2095-9907
    DOI 10.1038/s41392-022-01142-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: T-cell immunity

    Fei Yu / Wanbo Tai / Gong Cheng

    Signal Transduction and Targeted Therapy, Vol 7, Iss 1, Pp 1-

    a barrier to Omicron immune evasion

    2022  Volume 3

    Keywords Medicine ; R ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Development of a ferritin-based nanoparticle vaccine against the SARS-CoV-2 Omicron variant.

    Tai, Wanbo / Chai, Benjie / Feng, Shengyong / Zhuang, Xinyu / Ma, Jun / Pang, Mujia / Pan, Lin / Yang, Zi / Tian, Mingyao / Cheng, Gong

    Signal transduction and targeted therapy

    2022  Volume 7, Issue 1, Page(s) 173

    MeSH term(s) COVID-19/prevention & control ; Ferritins/genetics ; Humans ; Nanoparticles ; SARS-CoV-2 ; Viral Vaccines
    Chemical Substances Viral Vaccines ; Ferritins (9007-73-2)
    Language English
    Publishing date 2022-06-01
    Publishing country England
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 2886872-9
    ISSN 2059-3635 ; 2095-9907
    ISSN (online) 2059-3635
    ISSN 2095-9907
    DOI 10.1038/s41392-022-01041-8
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  5. Article ; Online: Advances in mRNA and other vaccines against MERS-CoV.

    Tai, Wanbo / Zhang, Xiujuan / Yang, Yang / Zhu, Jiang / Du, Lanying

    Translational research : the journal of laboratory and clinical medicine

    2021  Volume 242, Page(s) 20–37

    Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human coronavirus (CoV). Belonging to the same beta-CoV genus as severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and SARS-CoV-2, MERS-CoV has a significantly ... ...

    Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic human coronavirus (CoV). Belonging to the same beta-CoV genus as severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and SARS-CoV-2, MERS-CoV has a significantly higher fatality rate with limited human-to-human transmissibility. MERS-CoV causes sporadic outbreaks, but no vaccines have yet been approved for use in humans, thus calling for continued efforts to develop effective vaccines against this important CoV. Similar to SARS-CoV-1 and SARS-CoV-2, MERS-CoV contains 4 structural proteins, among which the surface spike (S) protein has been used as a core component in the majority of currently developed MERS-CoV vaccines. Here, we illustrate the importance of the MERS-CoV S protein as a key vaccine target and provide an update on the currently developed MERS-CoV vaccines, including those based on DNAs, proteins, virus-like particles or nanoparticles, and viral vectors. Additionally, we describe approaches for designing MERS-CoV mRNA vaccines and explore the role and importance of naturally occurring pseudo-nucleosides in the design of effective MERS-CoV mRNA vaccines. This review also provides useful insights into designing and evaluating mRNA vaccines against other viral pathogens.
    MeSH term(s) COVID-19 ; Humans ; Middle East Respiratory Syndrome Coronavirus/genetics ; RNA, Messenger ; SARS-CoV-2 ; Viral Vaccines
    Chemical Substances RNA, Messenger ; Viral Vaccines
    Language English
    Publishing date 2021-11-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2246684-8
    ISSN 1878-1810 ; 1532-6543 ; 1931-5244
    ISSN (online) 1878-1810 ; 1532-6543
    ISSN 1931-5244
    DOI 10.1016/j.trsl.2021.11.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Ud II Zs 42: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Development of a ferritin-based nanoparticle vaccine against the SARS-CoV-2 Omicron variant

    Wanbo Tai / Benjie Chai / Shengyong Feng / Xinyu Zhuang / Jun Ma / Mujia Pang / Lin Pan / Zi Yang / Mingyao Tian / Gong Cheng

    Signal Transduction and Targeted Therapy, Vol 7, Iss 1, Pp 1-

    2022  Volume 3

    Keywords Medicine ; R ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: MERS-CoV RBD-mRNA vaccine induces potent and broadly neutralizing antibodies with protection against MERS-CoV infection.

    Tai, Wanbo / Zheng, Jian / Zhang, Xiujuan / Shi, Juan / Wang, Gang / Guan, Xiaoqing / Zhu, Jiang / Perlman, Stanley / Du, Lanying

    Virus research

    2023  Volume 334, Page(s) 199156

    Abstract: Middle East respiratory syndrome coronavirus (MERS-CoV), a highly pathogenic coronavirus in the same Betacoronavirus genus and Coronaviridae family as SARS-CoV-2, continues to post a threat to human health. Mortality remains high; therefore, there is a ... ...

    Abstract Middle East respiratory syndrome coronavirus (MERS-CoV), a highly pathogenic coronavirus in the same Betacoronavirus genus and Coronaviridae family as SARS-CoV-2, continues to post a threat to human health. Mortality remains high; therefore, there is a need to develop effective vaccines to prevent MERS-CoV infection. The receptor-binding domain (RBD) within the MERS-CoV spike (S) protein is a critical vaccine target. The latest mRNA technology has enabled rapid development of much-needed vaccines with high efficiency and scalable manufacturing capacity. Here, we designed a mRNA vaccine encoding the RBD of MERS-CoV S protein (RBD-mRNA) and evaluated its immunogenicity and protective efficacy in a mouse model. The data showed that nucleoside-modified RBD-mRNA, but not RBD-mRNA lacking the nucleoside modification, was stable and elicited broadly and durable neutralizing antibody and cellular immune responses, which neutralized the original strain and multiple MERS-CoV variants. Among all immunization routes tested, the intradermal route was appropriate for this RBD-mRNA to induce strong B-cell responses and the highest neutralizing antibody titers. Importantly, injection of nucleoside-modified RBD-mRNA through the intradermal route protected immunized mice against challenge with MERS-CoV. This protection correlated with serum neutralizing antibody titers. Overall, we have developed an effective MERS-CoV RBD-based mRNA vaccine (with potential for further development) that prevents infection by divergent strains of MERS-CoV.
    MeSH term(s) Mice ; Humans ; Animals ; Middle East Respiratory Syndrome Coronavirus/chemistry ; Broadly Neutralizing Antibodies ; Antibodies, Viral ; Nucleosides ; COVID-19 ; SARS-CoV-2 ; Antibodies, Neutralizing ; Viral Vaccines/genetics ; Spike Glycoprotein, Coronavirus/chemistry ; Mice, Inbred BALB C
    Chemical Substances Broadly Neutralizing Antibodies ; Antibodies, Viral ; Nucleosides ; Antibodies, Neutralizing ; Viral Vaccines ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2023-06-19
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 605780-9
    ISSN 1872-7492 ; 0168-1702
    ISSN (online) 1872-7492
    ISSN 0168-1702
    DOI 10.1016/j.virusres.2023.199156
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1965: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
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  8. Article ; Online: SARS-CoV-2 infection induces testicular injury in Rhesus macaque.

    Liang, Mengying / Tai, Wanbo / Wang, Yunyun / Dai, Yulong / Yao, Yanfeng / Min, Juan / Zhou, Yiwu / Liu, Liang / Shan, Chao / Xia, Han / Yuan, Zhiming

    Virologica Sinica

    2022  

    Language English
    Publishing date 2022-10-28
    Publishing country Netherlands
    Document type Letter
    ZDB-ID 1011219-4
    ISSN 1995-820X ; 1000-3223 ; 1003-5125
    ISSN (online) 1995-820X
    ISSN 1000-3223 ; 1003-5125
    DOI 10.1016/j.virs.2022.10.008
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    Zs.A 4175: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  9. Article ; Online: A T cell-based SARS-CoV-2 spike protein vaccine provides protection without antibodies.

    Shi, Juan / Zheng, Jian / Zhang, Xiujuan / Tai, Wanbo / Compas, Ryan / Deno, Jack / Jachym, Natalie / Verma, Abhishek K / Wang, Gang / Guan, Xiaoqing / Odle, Abby E / Wan, Yushun / Li, Fang / Perlman, Stanley / Qiao, Liang / Du, Lanying

    JCI insight

    2024  Volume 9, Issue 5

    Abstract: SARS-CoV-2 spike-based vaccines are used to control the COVID-19 pandemic. However, emerging variants have become resistant to antibody neutralization and further mutations may lead to full resistance. We tested whether T cells alone could provide ... ...

    Abstract SARS-CoV-2 spike-based vaccines are used to control the COVID-19 pandemic. However, emerging variants have become resistant to antibody neutralization and further mutations may lead to full resistance. We tested whether T cells alone could provide protection without antibodies. We designed a T cell-based vaccine in which SARS-CoV-2 spike sequences were rearranged and attached to ubiquitin. Immunization of mice with the vaccine induced no specific antibodies, but strong specific T cell responses. We challenged mice with SARS-CoV-2 wild-type strain or an Omicron variant after the immunization and monitored survival or viral titers in the lungs. The mice were significantly protected against death and weight loss caused by the SARS-CoV-2 wild-type strain, and the viral titers in the lungs of mice challenged with the SARS-CoV-2 wild-type strain or the Omicron variant were significantly reduced. Importantly, depletion of CD4+ or CD8+ T cells led to significant loss of the protection. Our analyses of spike protein sequences of the variants indicated that fewer than one-third presented by dominant HLA alleles were mutated and that most of the mutated epitopes were in the subunit 1 region. As the subunit 2 region is conservative, the vaccines targeting spike protein are expected to protect against future variants due to the T cell responses.
    MeSH term(s) Animals ; Humans ; Mice ; Spike Glycoprotein, Coronavirus/genetics ; Pandemics ; COVID-19/prevention & control ; SARS-CoV-2 ; Antibodies ; Vaccines ; COVID-19 Vaccines
    Chemical Substances spike protein, SARS-CoV-2 ; Spike Glycoprotein, Coronavirus ; Antibodies ; Vaccines ; COVID-19 Vaccines
    Language English
    Publishing date 2024-03-08
    Publishing country United States
    Document type Journal Article
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.155789
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  10. Article ; Online: The Potency of an Anti-MERS Coronavirus Subunit Vaccine Depends on a Unique Combinatorial Adjuvant Formulation

    Parakkal Jovvian George / Wanbo Tai / Lanying Du / Sara Lustigman

    Vaccines, Vol 8, Iss 251, p

    2020  Volume 251

    Abstract: Vaccination is one of the most successful strategies to prevent human infectious diseases. Combinatorial adjuvants have gained increasing interest as they can stimulate multiple immune pathways and enhance the vaccine efficacy of subunit vaccines. We ... ...

    Abstract Vaccination is one of the most successful strategies to prevent human infectious diseases. Combinatorial adjuvants have gained increasing interest as they can stimulate multiple immune pathways and enhance the vaccine efficacy of subunit vaccines. We investigated the adjuvanticity of Aluminum (alum) in combination with rASP-1, a protein adjuvant, using the Middle East respiratory syndrome coronavirus MERS-CoV receptor-binding-domain (RBD) vaccine antigen. A highly enhanced anti-MERS-CoV neutralizing antibody response was induced when mice were immunized with rASP-1 and the alum-adjuvanted RBD vaccine in two separate injection sites as compared to mice immunized with RBD + rASP-1 + alum formulated into a single inoculum. The antibodies produced also significantly inhibited the binding of RBD to its cell-associated receptor. Moreover, immunization with rASP-1 co-administered with the alum-adjuvanted RBD vaccine in separate sites resulted in an enhanced frequency of TfH and GC B cells within the draining lymph nodes, both of which were positively associated with the titers of the neutralizing antibody response related to anti-MERS-CoV protective immunity. Our findings not only indicate that this unique combinatorial adjuvanted RBD vaccine regimen improved the immunogenicity of RBD, but also point to the importance of utilizing combinatorial adjuvants for the induction of synergistic protective immune responses.
    Keywords adjuvants ; adjuvant combination ; aluminum ; rASP-1 ; synergy ; MERS-CoV ; Medicine ; R
    Subject code 570 ; 630
    Language English
    Publishing date 2020-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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