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- Humbert, Marion, et al.
(author)
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Functional SARS-CoV-2 cross-reactive CD4+ T cells established in early childhood decline with age
- 2023
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In: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 120:12
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Journal article (peer-reviewed)abstract
- Pre-existing SARS-CoV-2-reactive T cells have been identified in SARS-CoV-2-unexposed individuals, potentially modulating COVID-19 and vaccination outcomes. Here, we provide evidence that functional cross-reactive memory CD4+ T cell immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is established in early childhood, mirroring early seroconversion with seasonal human coronavirus OC43. Humoral and cellular immune responses against OC43 and SARS-CoV-2 were assessed in SARS-CoV-2-unexposed children (paired samples at age two and six) and adults (age 26 to 83). Pre-existing SARS-CoV-2-reactive CD4+ T cell responses targeting spike, nucleocapsid, and membrane were closely linked to the frequency of OC43-specific memory CD4+ T cells in childhood. The functional quality of the cross-reactive memory CD4+ T cell responses targeting SARS-CoV-2 spike, but not nucleocapsid, paralleled OC43-specific T cell responses. OC43-specific antibodies were prevalent already at age two. However, they did not increase further with age, contrasting with the antibody magnitudes against HKU1 (β-coronavirus), 229E and NL63 (α-coronaviruses), rhinovirus, Epstein–Barr virus (EBV), and influenza virus, which increased after age two. The quality of the memory CD4+ T cell responses peaked at age six and subsequently declined with age, with diminished expression of interferon (IFN)-γ, interleukin (IL)-2, tumor necrosis factor (TNF), and CD38 in late adulthood. Age-dependent qualitative differences in the pre-existing SARS-CoV-2-reactive T cell responses may reflect the ability of the host to control coronavirus infections and respond to vaccination. Copyright © 2023 the Author(s).
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2. |
- Svedberg, Gustav, 1989-
(author)
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Novel planar and particle-based microarrays for point-of-care diagnostics
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Point-of-care assays are easy-to-use, portable and inexpensive tests that canbe used to aid diagnostics by measuring levels of disease-specific moleculesin settings where access to advanced laboratory equipment and trainedpersonnel are limited, such as at the patient's bedside or in low resourceparts of developing countries. In order to achieve high multiplexingcapacities, such assays can be based on planar microarrays consisting ofspots immobilized on a flat surface or on particle-based microarrays basedon populations of encoded particles. The aim of the work presented in thisthesis is to develop new point-of-care amenable planar and particle-basedmicroarrays that allow for highly multiplexed assays while maintaining lowsample-to-result times, complexity and instrumentation requirements.Paper I demonstrates the use graphically encoded particles for colorimetricdetection of autoantibodies using a consumer-grade flatbed scanner. Fourgraphical characters on the surface of each particle allows for millions ofcodes and the use of gold nanoparticles as a detection label allows both thecode and the signal intensity to be read out in a single image.Paper II describes a signal enhancement method that increases thesensitivity of gold nanoparticle detection on planar microarrays. Using thismethod, detection of allergen-specific IgE can be carried out using aconsumer-grade flatbed scanner instead of a more expensive fluorescencescanner without sacrificing assay performance.Paper III demonstrates the use of an isothermal DNA amplification methodfor detection of adenoviral DNA on a paper-based microarray. Using anisothermal amplification method eliminates the need for a thermocycler,reducing the instrumentation required for such detection.Paper IV shows the use of solid-phase PCR to amplify bacterial DNA directlyon the surface of particles. This strategy reduces assay time by eliminatingthe need for separate amplification and hybridisation steps.
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3. |
- Voskuil, Jan L. A., et al.
(author)
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The Antibody Society's antibody validation webinar series
- 2020
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In: mAbs. - : Informa UK Limited. - 1942-0862 .- 1942-0870. ; 12:1
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Journal article (peer-reviewed)abstract
- In the wake of the reproducibility crisis and numerous discussions on how commercially available antibodies as research tool contribute to it, The Antibody Society developed a series of 10 webinars to address the issues involved. The webinars were delivered by speakers with both academic and commercial backgrounds. This report highlights the problems, and offers solutions to help the scientific community appropriately identify the right antibodies and to validate them for their research and development projects. Despite the various solutions proposed here, they must be applied on a case-by-case basis. Each antibody must be verified based on the content of the product sheet, and subsequently through experimentation to confirm integrity, specificity and selectivity. Verification needs to focus on the precise application and tissue/cell type for which the antibody will be used, and all verification data must be reported openly. The various approaches discussed here all have caveats, so a combination of solutions must be considered.
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