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- Al-Dury, Samer, et al.
(author)
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Impaired SARS-CoV-2-specific T-cell reactivity in patients with cirrhosis following mRNA COVID-19 vaccination
- 2022
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In: JHEP Reports. - : Elsevier BV. - 2589-5559. ; 4:7
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Journal article (peer-reviewed)abstract
- Background & Aims: Cirrhosis entails elevated risk of COVID-19-associated mortality. This study determined T cell-mediated and antibody reactivity against the spike 1 (S1) protein of SARS-CoV-2 among 48 patients with cirrhosis and 39 healthy controls after mRNA COVID-19 vaccination. Methods: SARS-CoV-2-specific T-cell reactivity was measured by induced level of T cell-derived interferon-gamma (IFN-gamma) in blood cells stimulated ex vivo with multimeric peptides spanning the N-terminal portion of S1. S1-induced IFN-gamma was quantified before and after the 1st and 2nd vaccination (BNT162b2, Pfizer-BioNTech or mRNA-1273, Moderna) alongside serum IgG against the receptor-binding domain (RBD) within S1 (anti-RBD-S1 IgG). Results: T-cell reactivity against S1 was reduced in patients with cirrhosis after the 1st (p < 0.001 vs. controls) and 2nd (p < 0.001) vaccination. Sixty-eight percent of patients lacked detectable S1-specific T-cell reactivity after the 1st vaccination vs. 19% in controls (odds ratio 0.11, 95% CI 0.03-0.48, p = 0.003) and 36% remained devoid of reactivity after the 2nd vaccination vs. 6% in controls (odds ratio 0.12, 95% CI 0.03-0.59, p = 0.009). T-cell reactivity in cirrhosis remained significantly impaired after correction for potential confounders in multivariable analysis. Advanced cirrhosis (Child-Pugh class B) was associated with absent or lower T-cell responses (p < 0.05 vs. Child-Pugh class A). The deficiency of T-cell reactivity was paralleled by lower levels of anti-RBD-S1 IgG after the 1st (p < 0.001 vs. controls) and 2nd (p < 0.05) vaccination. Conclusions: Patients with cirrhosis show deficient T-cell reactivity against SARS-CoV-2 antigens along with diminished levels of anti-RBD-S1 IgG after dual COVID-19 vaccination, highlighting the need for vigilance and additional preventative measures. Clinical trial registration: EudraCT 2021-000349-42 Lay summary: T cells are a pivotal component in the defence against viruses. We show that patients with cirrhosis have impaired SARS-CoV-2-specific T-cell responses and lower antibody levels after mRNA vaccination against COVID-19 compared with healthy controls. Patients with more advanced liver disease exhibited particularly inferior vaccine responses. These results call for additional preventative measures in these patients. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).
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- Arabpour, Mohammad, et al.
(author)
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ADP-ribosylating adjuvant reveals plasticity in cDC1 cells that drive mucosal Th17 cell development and protection against influenza virus infection
- 2022
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In: Mucosal Immunology. - : Elsevier BV. - 1933-0219. ; 15:4, s. 745-761
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Journal article (peer-reviewed)abstract
- Migratory dendritic cells expressing CD103 are the targets for mucosal vaccines. These belong to either of two lineage-restricted subsets, cDC1 or cDC2 cells, which have been linked to priming of functionally distinct CD4 T cells. However, recent studies have identified plasticity in cDC2 cells with overlapping functions with cDC1 cells, while the converse has not been reported. We genetically engineered a vaccine adjuvant platform that targeted the cholera toxin A1 (CTA1) ADP-ribosylating enzyme to CD103(+) cDC1 and cDC2 cells using a single-chain antibody (scFv) to CD103. Unexpectedly, intranasal immunization with the CTA1-svFcCD103 adjuvant modified cDC1 cells to effectively prime Th17 cells, a function previously limited to cDC2 cells. In fact, cDC2 cells were dispensible, while cDC1 cells, lacking in Batf3-/- mice, were critical. Following intranasal immunizations isolated cDC1 cells from mLN exclusively promoted Rorgt(+) T cells and IL-17, IL-21, and IL-22 production. Strong CD8 T cell responses through antigen cross presentation by cDC1 cells were also observed. Single-cell RNAseq analysis revealed upregulation of Th17-promoting gene signatures in sorted cDC1 cells. Gene expression in isolated cDC2 cells was largely unaffected. Our finding represents a major shift of paradigm as we have documented functional plasticity in cDC1 cells.
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- Ghoreishi, Farzaneh S., et al.
(author)
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Enhancing the efficiency and stability of perovskite solar cells based on moisture-resistant dopant free hole transport materials by using a 2D-BA2PbI4 interfacial layer
- 2022
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In: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 24:3, s. 1675-1684
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Journal article (peer-reviewed)abstract
- In this work, the photovoltaic performance and stability of perovskite solar cells (PSCs) based on a dopant-free hole transport layer (HTL) are efficiently improved by inserting a two-dimensional (2D) interfacial layer. The benzyl ammonium lead iodide (BA2PbI4) 2D perovskite is used as an interfacial layer between the 3D CH3NH3PbI3 perovskite and two moisture-resistant dopant-free HTLs including poly[[2,3-bis(3-octyloxyphenyl)-5,8-quinoxalinediyl]-2,5-thiophenediyl] (TQ1) and poly(3-hexylthiophene) (P3HT). TQ1 with a facile synthesis procedure has a higher moisture resistivity compared to P3HT which can improve the stability of PSCs. The 2D BA2PbI4 perovskite with a less-volatile bulkier organic cation efficiently passivates the defects at the perovskite/HTL interface, leading to 11.95% and 15.04% efficiency for the modified TQ1 and P3HT based cells, respectively. For a better understanding, the structural, optical, and electrical properties of PSCs comprising P3HT and TQ1 HTLs with and without interface modification are studied. The interface modified PSCs show slower open-circuit voltage decay and longer carrier lifetimes compared to unmodified cells. In addition, impedance spectroscopy reveals lower charge transport resistance and higher recombination resistance for the modified devices, which could be associated with the modification of the interface between the 3D CH3NH3PbI3 perovskite and HTL caused by the 2D interfacial layer. Also after aging under ambient conditions for about 800 hours, the modified PCSs retain more than 80% of their initial PCEs. These results give us the hope of achieving simpler, cheaper, and more stable PSCs with dopant-free HTLs through 2D interfacial layers, which have great potential for commercialization.
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- Martner, Anna, 1979, et al.
(author)
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Transient and durable T cell reactivity after COVID-19
- 2022
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 119:30
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Journal article (peer-reviewed)abstract
- This study analyzed whole blood samples (n = 56) retrieved from 30 patients at 1 to 21 (median 9) mo after verified COVID-19 to determine the polarity and duration of antigen-specific T cell reactivity against severe acute respiratory syndrome coronavirus 2-derived antigens. Multimeric peptides spanning the entire nucleocapsid protein triggered strikingly synchronous formation of interleukin (IL)-4, IL-12, IL-13, and IL-17 ex vivo until similar to 70 d after confirmed infection, whereafter this reactivity was no longer inducible. In contrast, levels of nucleocapsid-induced IL-2 and interferon-gamma remained stable and highly correlated at 3 to 21 mo after infection. Similar cytokine dynamics were observed in unvaccinated, convalescent patients using whole-blood samples stimulated with peptides spanning the N-terminal portion of the spike 1 protein. These results unravel two phases of T cell reactivity following natural COVID-19: an early, synchronous response indicating transient presence of multipolar, antigen-specific T helper (T-H) cells followed by an equally synchronous and durable T(H)1-like reactivity reflecting long-lasting T cell memory.
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