Frontiers in immunology
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Frontiers in immunology · Jan 2021
Observational StudyInduction of High Levels of Specific Humoral and Cellular Responses to SARS-CoV-2 After the Administration of Covid-19 mRNA Vaccines Requires Several Days.
In the context of the Covid-19 pandemic, the fast development of vaccines with efficacy of around 95% preventing Covid-19 illness provides a unique opportunity to reduce the mortality associated with the pandemic. However, in the absence of efficacious prophylactic medications and few treatments for this infection, the induction of a fast and robust protective immunity is required for effective disease control, not only to prevent the disease but also the infection and shedding/transmission. The objective of our study was to analyze the level of specific humoral and cellular T-cell responses against the spike protein of SARS-CoV-2 induced by two mRNA-based vaccines (BNT162b2 and mRNA-1273), but also how long it takes after vaccination to induce these protective humoral and cellular immune responses. ⋯ This refractory period in the induction of specific immunity observed after completing the vaccination could constitute a window of higher infection risk, which could explain some emerging cases of SARS-CoV-2 infection in vaccinated people.
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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
Cell-Mediated Immunity to NAGLU Transgene Following Intracerebral Gene Therapy in Children With Mucopolysaccharidosis Type IIIB Syndrome.
Mucopolysaccharidosis type IIIB syndrome (Sanfilippo disease) is a rare autosomic recessif disorder caused by mutations in the α-N-acetylglucosaminidase (NAGLU) gene coding for a lysosomal enzyme, leading to neurodegeneration and progressive deterioration of cognitive abilities in affected children. To supply the missing enzyme, several recent human gene therapy trials relied on the deposit of adeno-associated virus (AAV) vectors directly into the brain. We reported safety and efficacy of an intracerebral therapy in a phase 1/2 clinical trial (https://clinicaltrials.gov/ct2/show/NCT03300453), with a recombinant AAV serotype 2/5 (rAAV2/5) coding human NAGLU in four children with MPS IIIB syndrome receiving immunosuppression. ⋯ We also report that gene therapy did not trigger neuroinflammation, evaluated through the expression of cytokines and chemokines in patients' CSF. Milder disease progression in the youngest patient was found associated with low level and less differentiated circulating NAGLU-specific T cells, together with the lack of proinflammatory cytokines in the CSF. Findings in this study support a systematic and comprehensive immunomonitoring approach for understanding the impact immune reactions might have on treatment safety and efficacy of gene therapies.
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Frontiers in immunology · Jan 2021
Vaccine Hesitancy and Rejection of a Vaccine for the Novel Coronavirus in the United States.
The arrival of the COVID-19 vaccine has been accompanied by increased discussion of vaccine hesitancy. However, it is unclear if there are shared patterns between general vaccine hesitancy and COVID-19 vaccine rejection, or if these are two different concepts. This study characterized rejection of a hypothetical COVID-19 vaccine, and compared patterns of association between general vaccine hesitancy and COVID-19 vaccine rejection. ⋯ During the COVID-19 epidemic's early phase, patterns of vaccine hesitancy and COVID-19 vaccine rejection were relatively similar. A significant minority would reject a COVID-19 vaccine, especially one with less-than-ideal effectiveness. Preparations for introducing the COVID-19 vaccine should anticipate substantial hesitation and target concerns, especially among younger adults.
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Frontiers in immunology · Jan 2021
Phenotype, Susceptibility, Autoimmunity, and Immunotherapy Between Kawasaki Disease and Coronavirus Disease-19 Associated Multisystem Inflammatory Syndrome in Children.
Coronavirus disease-19 (COVID-19) in children is usually mild but some are susceptible to a Kawasaki disease (KD)-like multisystem inflammatory syndrome in children (MIS-C) in the convalescent stage, posing a need to differentiate the phenotype, susceptibility, autoimmunity, and immunotherapy between KD and MIS-C, particularly in the upcoming mass vaccination of COVID-19. Patients with MIS-C are prone to gastrointestinal symptoms, coagulopathy, and shock in addition to atypical KD syndrome with fever, mucocutaneous lesions, lymphadenopathy, and/or cardiovascular events. MIS-C manifests KD-like symptoms that alert physicians to early recognize and adopt the KD treatment regimen for patients with MIS-C. ⋯ The evolution of immunotherapies for the diseases has shown that intravenous immunoglobulin (IVIG) alone or combined with corticosteroids is the standard treatment for KD, KDSS, and MIS-C. However, a certain portion of patients who revealed a treatment resistance to IVIG or IVIG plus corticosteroids, posing a need to early identify the immunopathogenesis, to protect hosts with genetic susceptibility, and to combat Th17/Treg imbalance by anti-cytokine or pro-Treg for reversal of the hyperinflammation and IVIG resistance. Based on physiological and pathological immunity of the diseases under genetic susceptibility and host milieu conditions, a series of sequential regimens are provided to develop a so-called "Know thyself, enemy (pathogen), and ever-victorious" strategy for the prevention and immunotherapy of KD and/or MIS-C.