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  1. Article ; Online: Intranasal and intrapulmonary vaccination with an M protein-deficient respiratory syncytial virus (RSV) vaccine improves clinical signs and reduces viral replication in infant baboons after an RSV challenge infection.

    Ivanov, Vadim / Oomens, Antonius G P / Papin, James F / Staats, Rachel / Reuter, Darlene N / Yu, Zhongxin / Piedra, Pedro A / Wellliver, Robert C

    Vaccine

    2021  Volume 39, Issue 30, Page(s) 4063–4071

    Abstract: Respiratory syncytial virus (RSV) is the major viral respiratory pathogen for human infants and children. Despite a severe global burden incurred by annual RSV epidemics, there is no licensed RSV vaccine. We have developed an RSV vaccine from a human RSV ...

    Abstract Respiratory syncytial virus (RSV) is the major viral respiratory pathogen for human infants and children. Despite a severe global burden incurred by annual RSV epidemics, there is no licensed RSV vaccine. We have developed an RSV vaccine from a human RSV strain from which the gene for the viral M protein has been deleted ("Mnull RSV"). RSV infects airway cells and produces each of its proteins. The M protein is responsible for reassembling the various other synthesized viral proteins into new, intact virus. In the absence of the M protein, therefore, reassembly does not occur, and the Mnull RSV does not replicate. We vaccinated 2-week old infant baboons with Mnull RSV either intranasally (IN) or directly into the lung (intratracheal, or IT), then infected these animals by inoculating human RSV directly into the lung. IN vaccination induced inconsistent serum RSV neutralizing antibody (NA) responses, but provided moderate reductions in respiratory rates, overall signs of illness and viral replication in bronchoalveolar lavage (BAL) fluid following infection. Intratracheal vaccination induced much stronger RSV NA responses, which persisted for at least 4-6 months. Following RSV infection, animals vaccinated by the IT route had much greater reductions in tachypnea and work of breathing than animals vaccinated IN, and had undetectable amounts of virus in BAL fluids. These results support the further development of IT Mnull RSV vaccination to reduce the impact of RSV infection in humans.
    MeSH term(s) Animals ; Antibodies, Neutralizing ; Antibodies, Viral ; Child ; Humans ; Infant ; Papio ; Respiratory Syncytial Virus Infections/prevention & control ; Respiratory Syncytial Virus Vaccines ; Respiratory Syncytial Virus, Human ; Vaccination ; Virus Replication
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; Respiratory Syncytial Virus Vaccines
    Language English
    Publishing date 2021-06-14
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2021.06.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Intranasal and intrapulmonary vaccination with an M protein-deficient respiratory syncytial virus (RSV) vaccine improves clinical signs and reduces viral replication in infant baboons after an RSV challenge infection

    Ivanov, Vadim / Oomens, Antonius G.P. / Papin, James F. / Staats, Rachel / Reuter, Darlene N. / Yu, Zhongxin / Piedra, Pedro A. / Wellliver, Robert C.

    Vaccine. 2021 July 05, v. 39, no. 30 p.4063-4071

    2021  

    Abstract: Respiratory syncytial virus (RSV) is the major viral respiratory pathogen for human infants and children. Despite a severe global burden incurred by annual RSV epidemics, there is no licensed RSV vaccine. We have developed an RSV vaccine from a human RSV ...

    Abstract Respiratory syncytial virus (RSV) is the major viral respiratory pathogen for human infants and children. Despite a severe global burden incurred by annual RSV epidemics, there is no licensed RSV vaccine. We have developed an RSV vaccine from a human RSV strain from which the gene for the viral M protein has been deleted (“Mnull RSV”). RSV infects airway cells and produces each of its proteins. The M protein is responsible for reassembling the various other synthesized viral proteins into new, intact virus. In the absence of the M protein, therefore, reassembly does not occur, and the Mnull RSV does not replicate. We vaccinated 2-week old infant baboons with Mnull RSV either intranasally (IN) or directly into the lung (intratracheal, or IT), then infected these animals by inoculating human RSV directly into the lung. IN vaccination induced inconsistent serum RSV neutralizing antibody (NA) responses, but provided moderate reductions in respiratory rates, overall signs of illness and viral replication in bronchoalveolar lavage (BAL) fluid following infection. Intratracheal vaccination induced much stronger RSV NA responses, which persisted for at least 4–6 months. Following RSV infection, animals vaccinated by the IT route had much greater reductions in tachypnea and work of breathing than animals vaccinated IN, and had undetectable amounts of virus in BAL fluids. These results support the further development of IT Mnull RSV vaccination to reduce the impact of RSV infection in humans.
    Keywords Respiratory syncytial virus ; blood serum ; genes ; humans ; lungs ; pathogens ; protein deficiencies ; tachypnea ; vaccination ; vaccines ; virus replication ; viruses ; Mnull RSV accine ; RSV vaccine ; Infant baboon odel ; Bronchiolitis ; RSV ; Mnull RSV ; M ; BAL ; F ; FDA ; GMT ; IACUC ; IgG ; IM ; IN ; IT ; LRTI ; OUHSC ; PBS ; CI ; P
    Language English
    Dates of publication 2021-0705
    Size p. 4063-4071.
    Publishing place Elsevier Ltd
    Document type Article ; Online
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2021.06.013
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: CD151 Maintains Endolysosomal Protein Quality to Inhibit Vascular Inflammation.

    Chen, Junxiong / Ding, Yingjun / Jiang, Chao / Qu, Rongmei / Wren, Jonathan D / Georgescu, Constantin / Wang, Xuejun / Reuter, Darlene N / Liu, Beibei / Giles, Cory B / Mayr, Christoph H / Schiller, Herbert B / Dai, Jingxing / Stipp, Christopher S / Subramaniyan, Bharathiraja / Wang, Jie / Zuo, Houjuan / Huang, Chao / Fung, Kar-Ming /
    Rice, Heather C / Sonnenberg, Arnoud / Wu, David / Walters, Matthew S / Zhao, You-Yang / Kanie, Tomoharu / Hays, Franklin A / Papin, James F / Wang, Dao Wen / Zhang, Xin A

    Circulation research

    2024  Volume 134, Issue 10, Page(s) 1330–1347

    Abstract: Background: Tetraspanin CD151 is highly expressed in endothelia and reinforces cell adhesion, but its role in vascular inflammation remains largely unknown.: Methods: In vitro molecular and cellular biological analyses on genetically modified ... ...

    Abstract Background: Tetraspanin CD151 is highly expressed in endothelia and reinforces cell adhesion, but its role in vascular inflammation remains largely unknown.
    Methods: In vitro molecular and cellular biological analyses on genetically modified endothelial cells, in vivo vascular biological analyses on genetically engineered mouse models, and in silico systems biology and bioinformatics analyses on CD151-related events.
    Results: Endothelial ablation of
    Conclusions: Distinct from its canonical function in strengthening cell adhesion at cell surface, CD151 maintains endolysosome function by sustaining VCP/p97-mediated protein unfolding and turnover. By supporting protein quality control and protein degradation, CD151 prevents proteins from (1) buildup in endolysosomes and (2) discharge through exosomes, to limit vascular inflammation. Also, our study conceptualizes that balance between degradation and discharge of proteins in endothelial cells determines vascular information. Thus, the IFITM3/V-ATPase-tetraspanin-VCP/p97 complexes on endolysosome, as a protein quality control and inflammation-inhibitory machinery, could be beneficial for therapeutic intervention against vascular inflammation.
    MeSH term(s) Animals ; Lysosomes/metabolism ; Tetraspanin 24/metabolism ; Tetraspanin 24/genetics ; Humans ; Mice ; COVID-19/metabolism ; COVID-19/immunology ; COVID-19/pathology ; Endosomes/metabolism ; Mice, Knockout ; Vasculitis/metabolism ; Mice, Inbred C57BL ; SARS-CoV-2 ; Inflammation/metabolism ; Inflammation/pathology ; Sepsis/metabolism
    Chemical Substances Tetraspanin 24 ; CD151 protein, human
    Language English
    Publishing date 2024-04-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80100-8
    ISSN 1524-4571 ; 0009-7330 ; 0931-6876
    ISSN (online) 1524-4571
    ISSN 0009-7330 ; 0931-6876
    DOI 10.1161/CIRCRESAHA.123.323190
    Database MEDical Literature Analysis and Retrieval System OnLINE

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