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  1. Article: Immunogenicity and Efficacy of TNX-1800, A Live Virus Recombinant Poxvirus Vaccine Candidate, against SARS-CoV-2 Challenge in Nonhuman Primates.

    Awasthi, Mayanka / Macaluso, Anthony / Myscofski, Dawn / Prigge, Jon / Koide, Fusataka / Noyce, Ryan S / Fogarty, Siobhan / Stillwell, Helen / Goebel, Scott J / Daugherty, Bruce / Nasar, Farooq / Bavari, Sina / Lederman, Seth

    Vaccines

    2023  Volume 11, Issue 11

    Abstract: TNX-1800 is a synthetically derived live recombinant chimeric horsepox virus (rcHPXV) vaccine candidate expressing Wuhan SARS-CoV-2 spike (S) protein. The primary objective of this study was to evaluate the immunogenicity and efficacy of TNX-1800 in two ... ...

    Abstract TNX-1800 is a synthetically derived live recombinant chimeric horsepox virus (rcHPXV) vaccine candidate expressing Wuhan SARS-CoV-2 spike (S) protein. The primary objective of this study was to evaluate the immunogenicity and efficacy of TNX-1800 in two nonhuman primate species challenged with USA-WA1/2020 SARS-CoV-2. TNX-1800 vaccination was well tolerated with no serious adverse events or significant changes in clinical parameters. A single dose of TNX-1800 generated humoral responses in African Green Monkeys and Cynomolgus Macaques, as measured by the total binding of anti-SARS-CoV-2 S IgG and neutralizing antibody titers against the USA-WA1/2020 strain. In addition, a single dose of TNX-1800 induced an interferon-gamma (IFN-γ)-mediated T-cell response in Cynomolgus Macaques. Following challenge with SARS-CoV-2, African Green and Cynomolgus Macaques exhibited rapid clearance of virus in the upper and lower respiratory tract. Future studies will assess the efficacy of TNX-1800 against newly emerging variants and demonstrate its safety in humans.
    Language English
    Publishing date 2023-11-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines11111682
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Single Dose of Recombinant Chimeric Horsepox Virus (TNX-801) Vaccination Protects Macaques from Lethal Monkeypox Challenge.

    Noyce, Ryan S / Westfall, Landon W / Fogarty, Siobhan / Gilbert, Karen / Mpanju, Onesmo / Stillwell, Helen / Esparza, José / Daugherty, Bruce / Koide, Fusataka / Evans, David H / Lederman, Seth

    Viruses

    2023  Volume 15, Issue 2

    Abstract: The ongoing global Monkeypox outbreak that started in the spring of 2022 has reinforced the importance of protecting the population using live virus vaccines based on the vaccinia virus (VACV). Smallpox also remains a biothreat and although some U.S. ... ...

    Abstract The ongoing global Monkeypox outbreak that started in the spring of 2022 has reinforced the importance of protecting the population using live virus vaccines based on the vaccinia virus (VACV). Smallpox also remains a biothreat and although some U.S. military personnel are immunized with VACV, safety concerns limit its use in other vulnerable groups. Consequently, there is a need for an effective and safer, single dose, live replicating vaccine against both viruses. One potential approach is to use the horsepox virus (HPXV) as a vaccine. Contemporary VACV shares a common ancestor with HPXV, which from the time of Edward Jenner and through the 19th century, was extensively used to vaccinate against smallpox. However, it is unknown if early HPXV-based vaccines exhibited different safety and efficacy profiles compared to modern VACV. A deeper understanding of HPXV as a vaccine platform may allow the construction of safer and more effective vaccines against the poxvirus family. In a proof-of-concept study, we vaccinated cynomolgus macaques with TNX-801, a recombinant chimeric horsepox virus (rcHPXV), and showed that the vaccine elicited protective immune responses against a lethal challenge with monkeypox virus (MPXV), strain Zaire. The vaccine was well tolerated and protected animals from the development of lesions and severe disease. These encouraging data support the further development of TNX-801.
    MeSH term(s) Animals ; Orthopoxvirus/genetics ; Mpox (monkeypox)/prevention & control ; Smallpox/prevention & control ; Cowpox virus ; Poxviridae Infections/prevention & control ; Poxviridae Infections/veterinary ; Vaccination ; Vaccinia virus ; Variola virus ; Macaca fascicularis ; Vaccines, Attenuated
    Chemical Substances Vaccines, Attenuated
    Language English
    Publishing date 2023-01-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v15020356
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Type I interferon transcriptional network regulates expression of coinhibitory receptors in human T cells.

    Sumida, Tomokazu S / Dulberg, Shai / Schupp, Jonas C / Lincoln, Matthew R / Stillwell, Helen A / Axisa, Pierre-Paul / Comi, Michela / Unterman, Avraham / Kaminski, Naftali / Madi, Asaf / Kuchroo, Vijay K / Hafler, David A

    Nature immunology

    2022  Volume 23, Issue 4, Page(s) 632–642

    Abstract: Although inhibition of T cell coinhibitory receptors has revolutionized cancer therapy, the mechanisms governing their expression on human T cells have not been elucidated. In the present study, we show that type 1 interferon (IFN-I) regulates ... ...

    Abstract Although inhibition of T cell coinhibitory receptors has revolutionized cancer therapy, the mechanisms governing their expression on human T cells have not been elucidated. In the present study, we show that type 1 interferon (IFN-I) regulates coinhibitory receptor expression on human T cells, inducing PD-1/TIM-3/LAG-3 while inhibiting TIGIT expression. High-temporal-resolution mRNA profiling of IFN-I responses established the dynamic regulatory networks uncovering three temporal transcriptional waves. Perturbation of key transcription factors (TFs) and TF footprint analysis revealed two regulator modules with different temporal kinetics that control expression of coinhibitory receptors and IFN-I response genes, with SP140 highlighted as one of the key regulators that differentiates LAG-3 and TIGIT expression. Finally, we found that the dynamic IFN-I response in vitro closely mirrored T cell features in acute SARS-CoV-2 infection. The identification of unique TFs controlling coinhibitory receptor expression under IFN-I response may provide targets for enhancement of immunotherapy in cancer, infectious diseases and autoimmunity.
    MeSH term(s) COVID-19 ; Gene Regulatory Networks ; Humans ; Interferon Type I/genetics ; Receptors, Antigen, T-Cell/metabolism ; Receptors, Immunologic/genetics ; SARS-CoV-2 ; T-Lymphocytes
    Chemical Substances Interferon Type I ; Receptors, Antigen, T-Cell ; Receptors, Immunologic
    Language English
    Publishing date 2022-03-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/s41590-022-01152-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Order via subito

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  4. Article ; Online: Immunogenicity and Efficacy of TNX-1800, A Live Virus Recombinant Poxvirus Vaccine Candidate, Against SARS-CoV-2 Challenge in Nonhuman Primates

    Awasthi, Mayanka / Macaluso, Anthony / Myscofski, Dawn / Prigge, Jon / Koide, Fusataka / Noyce, Ryan S / Fogarty, Siobhan / Stillwell, Helen / Goebel, Scott J / Daugherty, Bruce / Nasar, Farooq / Bavari, Sina / Lederman, Seth

    bioRxiv

    Abstract: TNX-1800 is a synthetically derived live chimeric Horsepox Virus (rcHPXV) vaccine expressing Wuhan SARS-CoV-2 spike (S) protein. The primary objective of this study was to evaluate the immunogenicity and efficacy of TNX-1800 in two nonhuman primate ... ...

    Abstract TNX-1800 is a synthetically derived live chimeric Horsepox Virus (rcHPXV) vaccine expressing Wuhan SARS-CoV-2 spike (S) protein. The primary objective of this study was to evaluate the immunogenicity and efficacy of TNX-1800 in two nonhuman primate species challenged with USA-WA1/2020 SARS-CoV-2. TNX-1800 vaccination was well tolerated, as indicated by the lack of serious adverse events or significant changes in clinical parameters. A single dose of TNX-1800 generated robust humoral responses in African Green Monkeys and Cynomolgus Macaques, as measured by the total binding anti-SARS-CoV-2 S IgG and neutralizing antibody titers against the USA-WA1/2020 strain. In Cynomolgus Macaques, a single dose of TNX-1800 induced a strong interferon-gamma (IFN-γ) mediated T cell response, promoting both pathogen clearance in the upper and lower airways and generation of systemic neutralizing antibody response against WA strain SARS-CoV-2. Future studies will assess the efficacy of TNX-1800 against newly emerging variants and demonstrate its safety in humans.
    Keywords covid19
    Language English
    Publishing date 2023-09-20
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2023.09.19.558485
    Database COVID19

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  5. Article: Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells.

    Hafler, David / Sumida, Tomokazu / Dulberg, Shai / Schupp, Jonas / Stillwell, Helen / Axisa, Pierre-Paul / Comi, Michela / Lincoln, Matthew / Unterman, Avraham / Kaminski, Naftali / Madi, Asaf / Kuchroo, Vijay

    Research square

    2021  

    Abstract: While inhibition of T cell co-inhibitory receptors has revolutionized cancer therapy, the mechanisms governing their expression on human T cells have not been elucidated. Type 1 interferon (IFN-I) modulates T cell immunity in viral infection, ... ...

    Abstract While inhibition of T cell co-inhibitory receptors has revolutionized cancer therapy, the mechanisms governing their expression on human T cells have not been elucidated. Type 1 interferon (IFN-I) modulates T cell immunity in viral infection, autoimmunity, and cancer, and may facilitate induction of T cell exhaustion in chronic viral infection. Here we show that IFN-I regulates co-inhibitory receptor expression on human T cells, inducing PD-1/TIM-3/LAG-3 while surprisingly inhibiting TIGIT expression. High-temporal-resolution mRNA profiling of IFN-I responses enabled the construction of dynamic transcriptional regulatory networks uncovering three temporal transcriptional waves. Perturbation of key transcription factors on human primary T cells revealed unique regulators that control expression of co-inhibitory receptors. We found that the dynamic IFN-I response
    Language English
    Publishing date 2021-06-08
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-133494/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Type I Interferon Transcriptional Network Regulates Expression of Coinhibitory Receptors in Human T cells.

    Sumida, Tomokazu S / Dulberg, Shai / Schupp, Jonas / Stillwell, Helen A / Axisa, Pierre-Paul / Comi, Michela / Lincoln, Matthew / Unterman, Avraham / Kaminski, Naftali / Madi, Asaf / Kuchroo, Vijay K / Hafler, David A

    bioRxiv : the preprint server for biology

    2020  

    Abstract: While inhibition of T cell co-inhibitory receptors has revolutionized cancer therapy, the mechanisms governing their expression on human T cells have not been elucidated. Type 1 interferon (IFN-I) modulates T cell immunity in viral infection, ... ...

    Abstract While inhibition of T cell co-inhibitory receptors has revolutionized cancer therapy, the mechanisms governing their expression on human T cells have not been elucidated. Type 1 interferon (IFN-I) modulates T cell immunity in viral infection, autoimmunity, and cancer, and may facilitate induction of T cell exhaustion in chronic viral infection
    Keywords covid19
    Language English
    Publishing date 2020-10-31
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2020.10.30.362947
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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