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  1. Article: Drug resistant

    Schami, Alyssa / Islam, M Nurul / Wall, Matthew / Hicks, Amberlee / Meredith, Reagan / Kreiswirth, Barry / Mathema, Barun / Belisle, John T / Torrelles, Jordi B

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Mycobacterium tuberculosis (M.tb) ...

    Abstract Mycobacterium tuberculosis (M.tb)
    Language English
    Publishing date 2024-04-11
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.04.10.588986
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Age associated susceptibility to SARS-CoV-2 infection in the K18-hACE2 transgenic mouse model.

    Dwivedi, Varun / Shivanna, Vinay / Gautam, Shalini / Delgado, Jennifer / Hicks, Amberlee / Argonza, Marco / Meredith, Reagan / Turner, Joanne / Martinez-Sobrido, Luis / Torrelles, Jordi B / Kulkarni, Viraj

    GeroScience

    2024  Volume 46, Issue 3, Page(s) 2901–2913

    Abstract: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still an ongoing global health crisis. Clinical data indicate that the case fatality rate (CFR) is age dependent, with a higher CFR percentage ... ...

    Abstract Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still an ongoing global health crisis. Clinical data indicate that the case fatality rate (CFR) is age dependent, with a higher CFR percentage in the elderly population. We compared the pathogenesis of SARS-CoV-2 in young and aged K18-hACE2 transgenic mice. We evaluated morbidity, mortality, viral titers, immune responses, and histopathology in SARS-CoV-2-infected young and old K18-hACE2 transgenic mice. Within the limitation of having a low number of mice per group, our results indicate that SARS-CoV-2 infection resulted in slightly higher morbidity, mortality, and viral replication in the lungs of old mice, which was associated with an impaired IgM response and altered cytokine and chemokine profiles. Results of this study increase our understanding of SARS-CoV-2 infectivity and immuno-pathogenesis in the elderly population.
    MeSH term(s) Aged ; Animals ; Humans ; Mice ; COVID-19/immunology ; COVID-19/metabolism ; Cytokines ; Disease Models, Animal ; Mice, Transgenic ; SARS-CoV-2/pathogenicity ; Angiotensin-Converting Enzyme 2/genetics ; Immunoglobulin M
    Chemical Substances Cytokines ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Immunoglobulin M
    Language English
    Publishing date 2024-02-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2886586-8
    ISSN 2509-2723 ; 2509-2715
    ISSN (online) 2509-2723
    ISSN 2509-2715
    DOI 10.1007/s11357-024-01102-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1502: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article: Exposure of

    Allué-Guardia, Anna / Garcia-Vilanova, Andreu / Schami, Alyssa M / Olmo-Fontánez, Angélica M / Hicks, Amberlee / Peters, Jay / Maselli, Diego J / Wewers, Mark D / Wang, Yufeng / Torrelles, Jordi B

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Upon infection, : Importance: Tuberculosis, caused by airborne ... ...

    Abstract Upon infection,
    Importance: Tuberculosis, caused by airborne pathogen
    Language English
    Publishing date 2023-09-28
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.09.27.559381
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Human alveolar lining fluid from the elderly promotes Mycobacterium tuberculosis intracellular growth and translocation into the cytosol of alveolar epithelial cells.

    Olmo-Fontánez, Angélica M / Scordo, Julia M / Schami, Alyssa / Garcia-Vilanova, Andreu / Pino, Paula A / Hicks, Amberlee / Mishra, Richa / Jose Maselli, Diego / Peters, Jay I / Restrepo, Blanca I / Nargan, Kievershen / Naidoo, Threnesan / Clemens, Daniel L / Steyn, Adrie J C / Thacker, Vivek V / Turner, Joanne / Schlesinger, Larry S / Torrelles, Jordi B

    Mucosal immunology

    2024  Volume 17, Issue 2, Page(s) 155–168

    Abstract: The elderly population is highly susceptible to developing respiratory diseases, including tuberculosis, a devastating disease caused by the airborne pathogen Mycobacterium tuberculosis (M.tb) that kills one person every 18 seconds. Once M.tb reaches the ...

    Abstract The elderly population is highly susceptible to developing respiratory diseases, including tuberculosis, a devastating disease caused by the airborne pathogen Mycobacterium tuberculosis (M.tb) that kills one person every 18 seconds. Once M.tb reaches the alveolar space, it contacts alveolar lining fluid (ALF), which dictates host-cell interactions. We previously determined that age-associated dysfunction of soluble innate components in human ALF leads to accelerated M.tb growth within human alveolar macrophages. Here we determined the impact of human ALF on M.tb infection of alveolar epithelial type cells (ATs), another critical lung cellular determinant of infection. We observed that elderly ALF (E-ALF)-exposed M.tb had significantly increased intracellular growth with rapid replication in ATs compared to adult ALF (A-ALF)-exposed bacteria, as well as a dampened inflammatory response. A potential mechanism underlying this accelerated growth in ATs was our observation of increased bacterial translocation into the cytosol, a compartment that favors bacterial replication. These findings in the context of our previous studies highlight how the oxidative and dysfunctional status of the elderly lung mucosa determines susceptibility to M.tb infection, including dampening immune responses and favoring bacterial replication within alveolar resident cell populations, including ATs, the most abundant resident cell type within the alveoli.
    MeSH term(s) Aged ; Adult ; Humans ; Mycobacterium tuberculosis ; Alveolar Epithelial Cells ; Cytosol ; Tuberculosis ; Lung/microbiology ; Macrophages, Alveolar
    Language English
    Publishing date 2024-01-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2411370-0
    ISSN 1935-3456 ; 1933-0219
    ISSN (online) 1935-3456
    ISSN 1933-0219
    DOI 10.1016/j.mucimm.2024.01.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6796: Show issues Location:
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  5. Article ; Online: Aerosolized sulfated hyaluronan derivatives prolong the survival of K18 ACE2 mice infected with a lethal dose of SARS-CoV-2.

    Pavan, Mauro / Fanti, Chiara D / Lucia, Alba Di / Canato, Elena / Acquasaliente, Laura / Sonvico, Fabio / Delgado, Jennifer / Hicks, Amberlee / Torrelles, Jordi B / Kulkarni, Viraj / Dwivedi, Varun / Zanellato, Anna M / Galesso, Devis / Pasut, Gianfranco / Buttini, Francesca / Martinez-Sobrido, Luis / Guarise, Cristian

    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences

    2023  Volume 187, Page(s) 106489

    Abstract: Despite several vaccines that are currently approved for human use to control the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an urgent medical need for therapeutic and prophylactic options. SARS-CoV-2 ... ...

    Abstract Despite several vaccines that are currently approved for human use to control the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an urgent medical need for therapeutic and prophylactic options. SARS-CoV-2 binding and entry in human cells involves interactions of its spike (S) protein with several host cell surface factors, including heparan sulfate proteoglycans (HSPGs), transmembrane protease serine 2 (TMPRSS2), and angiotensin-converting enzyme 2 (ACE2). In this paper we investigated the potential of sulphated Hyaluronic Acid (sHA), a HSPG mimicking polymer, to inhibit the binding of SARS-CoV-2 S protein to human ACE2 receptor. After the assessment of different sulfation degree of sHA backbone, a series of sHA functionalized with different hydrophobic side chains were synthesized and screened. The compound showing the highest binding affinity to the viral S protein was further characterized by surface plasmon resonance (SPR) towards ACE2 and viral S protein binding domain. Selected compounds were formulated as solutions for nebulization and, after being characterized in terms of aerosolization performance and droplet size distribution, their efficacy was assessed in vivo using the K18 human (h)ACE2 transgenic mouse model of SARS-CoV-2 infection.
    MeSH term(s) Animals ; Mice ; Humans ; SARS-CoV-2 ; COVID-19 ; Hyaluronic Acid ; Angiotensin-Converting Enzyme 2 ; Sulfates ; Mice, Transgenic
    Chemical Substances spike protein, SARS-CoV-2 ; Hyaluronic Acid (9004-61-9) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Sulfates ; K-18 conjugate
    Language English
    Publishing date 2023-06-11
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1154366-8
    ISSN 1879-0720 ; 0928-0987
    ISSN (online) 1879-0720
    ISSN 0928-0987
    DOI 10.1016/j.ejps.2023.106489
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3705: 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)
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  6. Article ; Online: Extracellular Delivery of Functional Mitochondria Rescues the Dysfunction of CD4

    Headley, Colwyn A / Gautam, Shalini / Olmo-Fontanez, Angelica / Garcia-Vilanova, Andreu / Dwivedi, Varun / Akhter, Anwari / Schami, Alyssa / Chiem, Kevin / Ault, Russell / Zhang, Hao / Cai, Hong / Whigham, Alison / Delgado, Jennifer / Hicks, Amberlee / Tsao, Philip S / Gelfond, Jonathan / Martinez-Sobrido, Luis / Wang, Yufeng / Torrelles, Jordi B /
    Turner, Joanne

    Advanced science (Weinheim, Baden-Wurttemberg, Germany)

    2023  Volume 11, Issue 5, Page(s) e2303664

    Abstract: Mitochondrial dysfunction alters cellular metabolism, increases tissue oxidative stress, and may be principal to the dysregulated signaling and function of ... ...

    Abstract Mitochondrial dysfunction alters cellular metabolism, increases tissue oxidative stress, and may be principal to the dysregulated signaling and function of CD4
    MeSH term(s) Humans ; Aged ; Mice ; Animals ; Aging ; CD4-Positive T-Lymphocytes ; T-Lymphocytes, Regulatory ; Mitochondria ; Mitochondrial Diseases
    Language English
    Publishing date 2023-11-21
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2808093-2
    ISSN 2198-3844 ; 2198-3844
    ISSN (online) 2198-3844
    ISSN 2198-3844
    DOI 10.1002/advs.202303664
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  7. Article: GMP Manufacturing and IND-Enabling Studies of a Recombinant Hyperimmune Globulin Targeting SARS-CoV-2

    Mizrahi, Rena A. / Lin, Wendy Y. / Gras, Ashley / Niedecken, Ariel R. / Wagner, Ellen K. / Keating, Sheila M. / Ikon, Nikita / Manickam, Vishal A. / Asensio, Michael A. / Leong, Jackson / Medina-Cucurella, Angelica V. / Benzie, Emily / Carter, Kyle P. / Chiang, Yao / Edgar, Robert C. / Leong, Renee / Lim, Yoong Wearn / Simons, Jan Fredrik / Spindler, Matthew J. /
    Stadtmiller, Kacy / Wayham, Nicholas / Büscher, Dirk / Terencio, Jose Vicente / Germanio, Clara Di / Chamow, Steven M. / Olson, Charles / Pino, Paula A. / Park, Jun-Gyu / Hicks, Amberlee / Ye, Chengjin / Garcia-Vilanova, Andreu / Martinez-Sobrido, Luis / Torrelles, Jordi B. / Johnson, David S. / Adler, Adam S.

    Pathogens. 2022 July 19, v. 11, no. 7

    2022  

    Abstract: Conventionally, hyperimmune globulin drugs manufactured from pooled immunoglobulins from vaccinated or convalescent donors have been used in treating infections where no treatment is available. This is especially important where multi-epitope ... ...

    Abstract Conventionally, hyperimmune globulin drugs manufactured from pooled immunoglobulins from vaccinated or convalescent donors have been used in treating infections where no treatment is available. This is especially important where multi-epitope neutralization is required to prevent the development of immune-evading viral mutants that can emerge upon treatment with monoclonal antibodies. Using microfluidics, flow sorting, and a targeted integration cell line, a first-in-class recombinant hyperimmune globulin therapeutic against SARS-CoV-2 (GIGA-2050) was generated. Using processes similar to conventional monoclonal antibody manufacturing, GIGA-2050, comprising 12,500 antibodies, was scaled-up for clinical manufacturing and multiple development/tox lots were assessed for consistency. Antibody sequence diversity, cell growth, productivity, and product quality were assessed across different manufacturing sites and production scales. GIGA-2050 was purified and tested for good laboratory procedures (GLP) toxicology, pharmacokinetics, and in vivo efficacy against natural SARS-CoV-2 infection in mice. The GIGA-2050 master cell bank was highly stable, producing material at consistent yield and product quality up to >70 generations. Good manufacturing practices (GMP) and development batches of GIGA-2050 showed consistent product quality, impurity clearance, potency, and protection in an in vivo efficacy model. Nonhuman primate toxicology and pharmacokinetics studies suggest that GIGA-2050 is safe and has a half-life similar to other recombinant human IgG1 antibodies. These results supported a successful investigational new drug application for GIGA-2050. This study demonstrates that a new class of drugs, recombinant hyperimmune globulins, can be manufactured consistently at the clinical scale and presents a new approach to treating infectious diseases that targets multiple epitopes of a virus.
    Keywords Severe acute respiratory syndrome coronavirus 2 ; cell growth ; cell lines ; drugs ; epitopes ; half life ; humans ; immunoglobulin G ; microfluidic technology ; models ; monoclonal antibodies ; neutralization ; pharmacokinetics ; product quality ; sequence diversity ; therapeutics ; toxicology ; viruses
    Language English
    Dates of publication 2022-0719
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens11070806
    Database NAL-Catalogue (AGRICOLA)

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  8. Article: GMP Manufacturing and IND-Enabling Studies of a Recombinant Hyperimmune Globulin Targeting SARS-CoV-2.

    Mizrahi, Rena A / Lin, Wendy Y / Gras, Ashley / Niedecken, Ariel R / Wagner, Ellen K / Keating, Sheila M / Ikon, Nikita / Manickam, Vishal A / Asensio, Michael A / Leong, Jackson / Medina-Cucurella, Angelica V / Benzie, Emily / Carter, Kyle P / Chiang, Yao / Edgar, Robert C / Leong, Renee / Lim, Yoong Wearn / Simons, Jan Fredrik / Spindler, Matthew J /
    Stadtmiller, Kacy / Wayham, Nicholas / Büscher, Dirk / Terencio, Jose Vicente / Germanio, Clara Di / Chamow, Steven M / Olson, Charles / Pino, Paula A / Park, Jun-Gyu / Hicks, Amberlee / Ye, Chengjin / Garcia-Vilanova, Andreu / Martinez-Sobrido, Luis / Torrelles, Jordi B / Johnson, David S / Adler, Adam S

    Pathogens (Basel, Switzerland)

    2022  Volume 11, Issue 7

    Abstract: Conventionally, hyperimmune globulin drugs manufactured from pooled immunoglobulins from vaccinated or convalescent donors have been used in treating infections where no treatment is available. This is especially important where multi-epitope ... ...

    Abstract Conventionally, hyperimmune globulin drugs manufactured from pooled immunoglobulins from vaccinated or convalescent donors have been used in treating infections where no treatment is available. This is especially important where multi-epitope neutralization is required to prevent the development of immune-evading viral mutants that can emerge upon treatment with monoclonal antibodies. Using microfluidics, flow sorting, and a targeted integration cell line, a first-in-class recombinant hyperimmune globulin therapeutic against SARS-CoV-2 (GIGA-2050) was generated. Using processes similar to conventional monoclonal antibody manufacturing, GIGA-2050, comprising 12,500 antibodies, was scaled-up for clinical manufacturing and multiple development/tox lots were assessed for consistency. Antibody sequence diversity, cell growth, productivity, and product quality were assessed across different manufacturing sites and production scales. GIGA-2050 was purified and tested for good laboratory procedures (GLP) toxicology, pharmacokinetics, and in vivo efficacy against natural SARS-CoV-2 infection in mice. The GIGA-2050 master cell bank was highly stable, producing material at consistent yield and product quality up to >70 generations. Good manufacturing practices (GMP) and development batches of GIGA-2050 showed consistent product quality, impurity clearance, potency, and protection in an in vivo efficacy model. Nonhuman primate toxicology and pharmacokinetics studies suggest that GIGA-2050 is safe and has a half-life similar to other recombinant human IgG1 antibodies. These results supported a successful investigational new drug application for GIGA-2050. This study demonstrates that a new class of drugs, recombinant hyperimmune globulins, can be manufactured consistently at the clinical scale and presents a new approach to treating infectious diseases that targets multiple epitopes of a virus.
    Language English
    Publishing date 2022-07-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens11070806
    Database MEDical Literature Analysis and Retrieval System OnLINE

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