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  1. Article ; Online: Does the Lectin Complement Pathway Link Kawasaki Disease and SARS-CoV-2?

    Polycarpou, Anastasia / Grigoriadou, Sofia / Klavinskis, Linda / Sacks, Steven

    Frontiers in immunology

    2021  Volume 11, Page(s) 604512

    MeSH term(s) COVID-19/complications ; COVID-19/immunology ; Child ; Child, Preschool ; Complement Pathway, Mannose-Binding Lectin/immunology ; Female ; Humans ; Male ; Mucocutaneous Lymph Node Syndrome/immunology ; SARS-CoV-2 ; Systemic Inflammatory Response Syndrome/immunology
    Language English
    Publishing date 2021-01-14
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.604512
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A timely update of global COVID-19 vaccine development.

    Klavinskis, Linda S / Liu, Margaret A / Lu, Shan

    Emerging microbes & infections

    2020  Volume 9, Issue 1, Page(s) 2379–2380

    Abstract: This commentary provides an overview and links to presentations of a recent virtual congress series organized by the International Society for Vaccines (ISV) focused on COVID-19 vaccines. The series provided the academic community and vaccine developers ... ...

    Abstract This commentary provides an overview and links to presentations of a recent virtual congress series organized by the International Society for Vaccines (ISV) focused on COVID-19 vaccines. The series provided the academic community and vaccine developers as well as the wider general public with balanced information of the global response and resources for COVID-19 vaccines under development featuring: 1) NGOs and the regulatory perspective, 2) the status of vaccine development efforts, and 3) panel discussions to present and discuss challenges. ISV is a non-profit scientific organization whose members work on all areas relevant to vaccines. ISV plans to host additional virtual symposia including regional meetings and incorporating other topics along with COVID-19 vaccines.
    MeSH term(s) Betacoronavirus/genetics ; Betacoronavirus/immunology ; COVID-19 ; COVID-19 Vaccines ; Coronavirus Infections/epidemiology ; Coronavirus Infections/genetics ; Coronavirus Infections/immunology ; Coronavirus Infections/prevention & control ; Coronavirus Infections/virology ; Drug Development/trends ; Humans ; Pandemics/prevention & control ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/prevention & control ; Pneumonia, Viral/virology ; SARS-CoV-2 ; Viral Vaccines/administration & dosage ; Viral Vaccines/genetics ; Viral Vaccines/immunology
    Chemical Substances COVID-19 Vaccines ; Viral Vaccines
    Keywords covid19
    Language English
    Publishing date 2020-10-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2681359-2
    ISSN 2222-1751 ; 2222-1751
    ISSN (online) 2222-1751
    ISSN 2222-1751
    DOI 10.1080/22221751.2020.1838246
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: A timely update of global COVID-19 vaccine development

    Klavinskis, Linda S / Liu, Margaret A / Lu, Shan

    Emerg Microbes Infect

    Abstract: This commentary provides an overview and links to presentations of a recent virtual congress series organized by the International Society for Vaccines (ISV) focused on COVID-19 vaccines. The series provided the academic community and vaccine developers ... ...

    Abstract This commentary provides an overview and links to presentations of a recent virtual congress series organized by the International Society for Vaccines (ISV) focused on COVID-19 vaccines. The series provided the academic community and vaccine developers as well as the wider general public with balanced information of the global response and resources for COVID-19 vaccines under development featuring: 1) NGOs and the regulatory perspective, 2) the status of vaccine development efforts, and 3) panel discussions to present and discuss challenges. ISV is a non-profit scientific organization whose members work on all areas relevant to vaccines. ISV plans to host additional virtual symposia including regional meetings and incorporating other topics along with COVID-19 vaccines.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #872908
    Database COVID19

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  4. Article ; Online: A timely update of global COVID-19 vaccine development

    Klavinskis, Linda S. / Liu, Margaret A. / Lu, Shan

    Emerging Microbes & Infections

    2020  Volume 9, Issue 1, Page(s) 2379–2380

    Keywords Immunology ; Epidemiology ; Microbiology ; Drug Discovery ; Parasitology ; Virology ; Infectious Diseases ; General Medicine ; covid19
    Language English
    Publisher Informa UK Limited
    Publishing country uk
    Document type Article ; Online
    ZDB-ID 2681359-2
    ISSN 2222-1751
    ISSN 2222-1751
    DOI 10.1080/22221751.2020.1838246
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Microneedle-mediated delivery of viral vectored vaccines.

    Zaric, Marija / Ibarzo Yus, Bárbara / Kalcheva, Petya Petrova / Klavinskis, Linda Sylvia

    Expert opinion on drug delivery

    2017  Volume 14, Issue 10, Page(s) 1177–1187

    Abstract: Introduction: Microneedle array platforms are a promising technology for vaccine delivery, due to their ease of administration with no sharp waste generated, small size, possibility of targeted delivery to the specified skin depth and efficacious ... ...

    Abstract Introduction: Microneedle array platforms are a promising technology for vaccine delivery, due to their ease of administration with no sharp waste generated, small size, possibility of targeted delivery to the specified skin depth and efficacious delivery of different vaccine formulations, including viral vectors. Areas covered: Attributes and challenges of the most promising viral vector candidates that have advanced to the clinic and that have been leveraged for skin delivery by microneedles; The importance of understanding the immunobiology of antigen-presenting cells in the skin, in particular dendritic cells, in order to generate further improved skin vaccination strategies; recent studies where viral vectors expressing various antigens have been coupled with microneedle technology to examine their potential for improved vaccination. Expert opinion: Simple, economic and efficacious vaccine delivery methods are needed to improve health outcomes and manage possible outbreaks of new emerging viruses. Understanding what innate/inflammatory signals are required to induce both immediate and long-term responses remains a major hurdle in the development of the effective vaccines. One approach to meet these needs is microneedle-mediated viral vector vaccination. In order for this technology to fulfil this potential the industry must invest significantly to further develop its design, production, biosafety, delivery and large-scale manufacturing.
    MeSH term(s) Animals ; Genetic Vectors ; Humans ; Microinjections ; Needles ; Vaccination/methods ; Vaccines/administration & dosage ; Viruses
    Chemical Substances Vaccines
    Language English
    Publishing date 2017
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2167286-6
    ISSN 1744-7593 ; 1742-5247
    ISSN (online) 1744-7593
    ISSN 1742-5247
    DOI 10.1080/17425247.2017.1230096
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Rationale for targeting complement in COVID-19.

    Polycarpou, Anastasia / Howard, Mark / Farrar, Conrad A / Greenlaw, Roseanna / Fanelli, Giorgia / Wallis, Russell / Klavinskis, Linda S / Sacks, Steven

    EMBO molecular medicine

    2020  Volume 12, Issue 8, Page(s) e12642

    Abstract: A novel coronavirus, SARS-CoV-2, has recently emerged in China and spread internationally, posing a health emergency to the global community. COVID-19 caused by SARS-CoV-2 is associated with an acute respiratory illness that varies from mild to the life- ... ...

    Abstract A novel coronavirus, SARS-CoV-2, has recently emerged in China and spread internationally, posing a health emergency to the global community. COVID-19 caused by SARS-CoV-2 is associated with an acute respiratory illness that varies from mild to the life-threatening acute respiratory distress syndrome (ARDS). The complement system is part of the innate immune arsenal against pathogens, in which many viruses can evade or employ to mediate cell entry. The immunopathology and acute lung injury orchestrated through the influx of pro-inflammatory macrophages and neutrophils can be directly activated by complement components to prime an overzealous cytokine storm. The manifestations of severe COVID-19 such as the ARDS, sepsis and multiorgan failure have an established relationship with activation of the complement cascade. We have collected evidence from all the current studies we are aware of on SARS-CoV-2 immunopathogenesis and the preceding literature on SARS-CoV-1 and MERS-CoV infection linking severe COVID-19 disease directly with dysfunction of the complement pathways. This information lends support for a therapeutic anti-inflammatory strategy against complement, where a number of clinically ready potential therapeutic agents are available.
    MeSH term(s) Adult ; Alveolar Epithelial Cells/immunology ; Alveolar Epithelial Cells/metabolism ; Alveolar Epithelial Cells/virology ; Angiotensin-Converting Enzyme 2 ; Animals ; Betacoronavirus/physiology ; COVID-19 ; Child ; Complement Activation/drug effects ; Complement C3b/antagonists & inhibitors ; Complement C3b/physiology ; Complement Inactivating Agents/pharmacology ; Complement Inactivating Agents/therapeutic use ; Coronavirus Infections/drug therapy ; Coronavirus Infections/immunology ; Cytokine Release Syndrome/drug therapy ; Cytokine Release Syndrome/etiology ; Cytokine Release Syndrome/immunology ; Glycosylation ; Humans ; Immunity, Innate ; Ligands ; Mice ; Models, Animal ; Models, Molecular ; Pandemics ; Pattern Recognition, Automated ; Peptidyl-Dipeptidase A/metabolism ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/immunology ; Protein Conformation ; Protein Processing, Post-Translational ; Receptors, Virus/metabolism ; Respiratory Distress Syndrome/etiology ; Respiratory Distress Syndrome/immunology ; SARS-CoV-2 ; Spike Glycoprotein, Coronavirus/chemistry ; Spike Glycoprotein, Coronavirus/metabolism ; COVID-19 Drug Treatment
    Chemical Substances Complement Inactivating Agents ; Ligands ; Receptors, Virus ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; Complement C3b (80295-43-8) ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Ace2 protein, mouse (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
    Keywords covid19
    Language English
    Publishing date 2020-07-12
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2467145-9
    ISSN 1757-4684 ; 1757-4676
    ISSN (online) 1757-4684
    ISSN 1757-4676
    DOI 10.15252/emmm.202012642
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    Zs.A 6784: Show issues Location:
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  7. Article ; Online: The complement pattern recognition molecule CL-11 promotes invasion and injury of respiratory epithelial cells by SARS-CoV-2.

    Polycarpou, Anastasia / Wagner-Gamble, Tara / Greenlaw, Roseanna / O'Neill, Lauren A. / Khan, Hataf / Malim, Michael M / Romano, Marco / Smolarek, Dorota / Doores, Katie J / Wallis, Russell / Klavinskis, Linda S / Sacks, Steven

    bioRxiv

    Abstract: Collectin-11 is a soluble C-type lectin produced at epithelial surfaces to initiate pathogen elimination by complement. Given the respiratory epithelium is a source of CL-11 and downstream complement-pathway components, we investigated the potential of ... ...

    Abstract Collectin-11 is a soluble C-type lectin produced at epithelial surfaces to initiate pathogen elimination by complement. Given the respiratory epithelium is a source of CL-11 and downstream complement-pathway components, we investigated the potential of CL-11 to impact the pathogenicity of SARS-CoV-2. While the SARS-CoV-2 spike trimer could bind CL-11 and trigger complement activation followed by MAC formation, the virus was resistant to lysis. Surprisingly, virus production by infected respiratory epithelial cells was enhanced by CL-11 opsonisation of virus but this effect was fully inhibited by sugar-blockade of CL-11. Moreover, SARS-CoV-2 spike protein expressed at the bronchial epithelial cell surface was associated with increased CL-11 binding and MAC formation. We propose that SARS-CoV-2 pathogenicity is exacerbated both by resistance to complement and CL-11 driven respiratory cell invasion and injury at the portal of entry. Contrary to expectation, CL-11 blockade could offer a novel approach to limit the pathogenicity of SARS-CoV-2.
    Keywords covid19
    Language English
    Publishing date 2023-12-12
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2023.12.11.571109
    Database COVID19

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  8. Article ; Online: The human intestinal IgA response; burning questions.

    Spencer, Jo / Klavinskis, Linda S / Fraser, Louise D

    Frontiers in immunology

    2012  Volume 3, Page(s) 108

    Abstract: The title of this special topic invites us to identify areas in the field of IgA biology that are uncertain or in need of clarification. The inductive phase of the human intestinal IgA response has been a controversial area for some years. Therefore, to ... ...

    Abstract The title of this special topic invites us to identify areas in the field of IgA biology that are uncertain or in need of clarification. The inductive phase of the human intestinal IgA response has been a controversial area for some years. Therefore, to structure this review, we have identified key questions that are debated in this field. We have provided explanations of the origins of the uncertainties and have provided our own reasoned answers to the questions we pose.
    Language English
    Publishing date 2012-05-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2012.00108
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  9. Article: Rationale for targeting complement in COVID-19

    Polycarpou, Anastasia / Howard, Mark / Farrar, Conrad A / Greenlaw, Roseanna / Fanelli, Giorgia / Wallis, Russell / Klavinskis, Linda S / Sacks, Steven

    EMBO Mol Med

    Abstract: A novel coronavirus, SARS-CoV-2, has recently emerged in China and spread internationally, posing a health emergency to the global community. COVID-19 caused by SARS-CoV-2 is associated with an acute respiratory illness that varies from mild to the life- ... ...

    Abstract A novel coronavirus, SARS-CoV-2, has recently emerged in China and spread internationally, posing a health emergency to the global community. COVID-19 caused by SARS-CoV-2 is associated with an acute respiratory illness that varies from mild to the life-threatening acute respiratory distress syndrome (ARDS). The complement system is part of the innate immune arsenal against pathogens, in which many viruses can evade or employ to mediate cell entry. The immunopathology and acute lung injury orchestrated through the influx of pro-inflammatory macrophages and neutrophils can be directly activated by complement components to prime an overzealous cytokine storm. The manifestations of severe COVID-19 such as the ARDS, sepsis and multiorgan failure have an established relationship with activation of the complement cascade. We have collected evidence from all the current studies we are aware of on SARS-CoV-2 immunopathogenesis and the preceding literature on SARS-CoV-1 and MERS-CoV infection linking severe COVID-19 disease directly with dysfunction of the complement pathways. This information lends support for a therapeutic anti-inflammatory strategy against complement, where a number of clinically ready potential therapeutic agents are available.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #607958
    Database COVID19

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  10. Article ; Online: Skin vaccination with live virus vectored microneedle arrays induce long lived CD8(+) T cell memory.

    Becker, Pablo D / Hervouet, Catherine / Mason, Gavin M / Kwon, Sung-Yun / Klavinskis, Linda S

    Vaccine

    2015  Volume 33, Issue 37, Page(s) 4691–4698

    Abstract: A simple dissolvable microneedle array (MA) platform has emerged as a promising technology for vaccine delivery, due to needle-free injection with a formulation that preserves the immunogenicity of live viral vectored vaccines dried in the MA matrix. ... ...

    Abstract A simple dissolvable microneedle array (MA) platform has emerged as a promising technology for vaccine delivery, due to needle-free injection with a formulation that preserves the immunogenicity of live viral vectored vaccines dried in the MA matrix. While recent studies have focused largely on design parameters optimized to induce primary CD8(+) T cell responses, the hallmark of a vaccine is synonymous with engendering long-lasting memory. Here, we address the capacity of dried MA vaccination to programme phenotypic markers indicative of effector/memory CD8(+) T cell subsets and also responsiveness to recall antigen benchmarked against conventional intradermal (ID) injection. We show that despite a slightly lower frequency of dividing T cell receptor transgenic CD8(+) T cells in secondary lymphoid tissue at an early time point, the absolute number of CD8(+) T cells expressing an effector memory (CD62L(-)CD127(+)) and central memory (CD62L(+)CD127(+)) phenotype during peak expansion were comparable after MA and ID vaccination with a recombinant human adenovirus type 5 vector (AdHu5) encoding HIV-1 gag. Similarly, both vaccination routes generated CD8(+) memory T cell subsets detected in draining LNs for at least two years post-vaccination capable of responding to secondary antigen. These data suggest that CD8(+) T cell effector/memory generation and long-term memory is largely unaffected by physical differences in vaccine delivery to the skin via dried MA or ID suspension.
    MeSH term(s) AIDS Vaccines/administration & dosage ; AIDS Vaccines/immunology ; Animals ; CD8-Positive T-Lymphocytes/immunology ; Drug Delivery Systems ; Immunologic Memory ; Injections, Intradermal ; Mice, Inbred C57BL ; Skin/immunology ; T-Lymphocyte Subsets/immunology ; Vaccines, Synthetic/administration & dosage
    Chemical Substances AIDS Vaccines ; Vaccines, Synthetic
    Language English
    Publishing date 2015-09-08
    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.2015.04.046
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