Frontiers in immunology
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Frontiers in immunology · Jan 2021
The Antigenicity of Epidemic SARS-CoV-2 Variants in the United Kingdom.
To determine whether the neutralization activity of monoclonal antibodies, convalescent sera and vaccine-elicited sera was affected by the top five epidemic SARS-CoV-2 variants in the UK, including D614G+L18F+A222V, D614G+A222V, D614G+S477N, VOC-202012/01(B.1.1.7) and D614G+69-70del+N439K, a pseudovirus-neutralization assay was performed to evaluate the relative neutralization titers against the five SARS-CoV-2 variants and 12 single deconvolution mutants based on the variants. In this study, 18 monoclonal antibodies, 10 sera from convalescent COVID-19 patients, 10 inactivated-virus vaccine-elicited sera, 14 mRNA vaccine-elicited sera, nine RBD-immunized mouse sera, four RBD-immunized horse sera, and four spike-encoding DNA-immunized guinea pig sera were tested and analyzed. ⋯ However, the convalescent sera, inactivated virus vaccine-elicited sera, mRNA vaccine-elicited sera, spike DNA-elicited sera, and recombinant RBD protein-elicited sera could still neutralize these variants (within three-fold changes compared to the reference D614G variant). The neutralizing antibody responses to different types of vaccines were different, whereby the response to inactivated-virus vaccine was similar to the convalescent sera.
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Frontiers in immunology · Jan 2021
Neuronal-Activated ILC2s Promote IL-17A Production in Lung γδ T Cells During Sepsis.
Studies have revealed important roles for IL-17A in the development of acute lung injury (ALI) following sepsis. However, the mechanism underlying the regulation of lung IL-17A remains to be fully addressed. Recent studies suggested the effect of neuromedin U (NMU) on immune cell activation and the role of group 2 innate lymphoid cells (ILC2s) in the modulation of IL-17A production. We aimed to gain in-depth insight into the mechanism underlying sepsis-induced lung IL-17A production, particularly, the role of NMU in mediating neuronal regulation of ILC2s and IL-17A-producing γδ T cells activation in sepsis. ⋯ In sepsis, NMU acting through NMUR1 in lung ILC2s initiates the ILC2 activation, which, in turn, promote IL-17A-producing γδ T cell expansion and secretion of IL-17A. ILC2-derived IL-9 plays an important role in mediating γδ T cell expansion and IL-17A production. This study explores a new mechanism underlying neuronal regulation of innate immunity in sepsis.
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Frontiers in immunology · Jan 2021
Comprehensive Comparison of RNA-Seq Data of SARS-CoV-2, SARS-CoV and MERS-CoV Infections: Alternative Entry Routes and Innate Immune Responses.
The pathogenesis of COVID-19 emerges as complex, with multiple factors leading to injury of different organs. Some of the studies on aspects of SARS-CoV-2 cell entry and innate immunity have produced seemingly contradictory claims. In this situation, a comprehensive comparative analysis of a large number of related datasets from several studies could bring more clarity, which is imperative for therapy development. ⋯ First, our analyses support the existence of cell entry mechanisms for SARS and SARS-CoV-2 other than the ACE2 route with evidence of inefficient infection of cells without expression of ACE2; expression of TMPRSS2/TPMRSS4 is unnecessary for efficient SARS-CoV-2 infection with evidence of efficient infection of A549 cells transduced with a vector expressing human ACE2. Second, we find that innate immune responses in terms of interferons and interferon simulated genes are strong in relevant cells, for example Calu3 cells, but vary markedly with cell type, virus dose, and virus type.
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Frontiers in immunology · Jan 2021
Integrating CAR T-Cell Therapy and Transplantation: Comparisons of Safety and Long-Term Efficacy of Allogeneic Hematopoietic Stem Cell Transplantation After CAR T-Cell or Chemotherapy-Based Complete Remission in B-Cell Acute Lymphoblastic Leukemia.
Patients often undergo consolidation allogeneic hematopoietic stem cell transplantation (allo-HSCT) to maintain long-term remission following chimeric antigen receptor (CAR) T-cell therapy. Comparisons of safety and efficacy of allo-HSCT following complete remission (CR) achieved by CAR-T therapy versus by chemotherapy for B-cell acute lymphoblastic leukemia (B-ALL) has not been reported. We performed a parallel comparison of transplant outcomes in 105 consecutive B-ALL patients who received allo-HSCT after achieving CR with CAR-T therapy (n=27) or with chemotherapy (n=78). ⋯ In conclusion, our data indicate that, in B-ALL patients, similar clinical safety outcomes could be achieved with either CD19 CAR T-cell therapy followed by allo-HSCT or chemotherapy followed by allo-HSCT. Despite the inclusion of more patients with advanced diseases in the CAR-T group, the 4-year LFS and OS achieved with CAR T-cells followed by allo-HSCT were as remarkable as those achieved with chemotherapy followed by allo-HSCT. Further confirmation of these results requires larger, randomized clinical trials.