Coronavac is a widely used SARS-CoV-2 inactivated vaccine, but its long-term immune response assessment is still lacking. We evaluated SARS-CoV-2-specific immune responses, including T cell activation markers, antigen-specific cytokine production and antibody response following vaccination in 53 adult and elderly individuals participating in a phase 3 clinical trial. Activated follicular helper T (Tfh), non-Tfh and memory CD4+ T cells were detected in almost all subjects early after the first vaccine dose. Activated memory CD4+ T cells were predominantly of central and effector memory T cell phenotypes and were sustained for at least 6 months. We also detected a balanced Th1-, Th2- and Th17/Th22-type cytokine production that was associated with response over time, together with particular cytokine profile linked to poor responses in older vaccinees. SARS-CoV-2-specific IgG levels peaked 14 days after the second dose and were mostly stable over one year. CoronaVac was able to induce a potent and durable antiviral antigen-specific cellular response and the cytokine profiles related to the response over time and impacted by the senescence were defined.
RESUMOApresenta-se, neste ensaio, uma revisão bibliográfica da produção sobre os legados de megaeventos esportivos, especificamente sobre a UEFA Eurocopa. Para levantamento da literatura, utilizaram-se as seguintes palavraschave: legados; legados esportivos; megaeventos; impactos de megaeventos; megaeventos esportivos; UEFA Euro; Eurocopa; e seus correspondentes no singular na língua espanhola e inglesa, por conveniência. As bases de dados foram: Annals; BVS; DOAJ; EBSCO; REDALYC; Periódicos CAPES; PubMed; Scielo; Scopus; Science Direct; e ScholarGoogle. Os resultados foram analisados em categorias. Verificou-se, entre outros fatores, que, no que se refere à Eurocopa, os legados correspondentes ao turismo, os impactos econômicos e o aspecto social vêm sendo discutidos com maior frequência, assim como as projeções e os prognósticos dos eventos que ocorreram posteriormente nas respectivas cidades-sede; verificou-se ainda que, em grande parte dos artigos, há a ausência de discussão sobre os impactos negativos de tais megaeventos. Recomenda-se a utilização de métodos padronizados, com comparações dos resultados e realização de estudos longitudinais, para melhor compreensão dos impactos e utilização dos legados.
O presente trabalho, uma pesquisa descritiva exploratória, tem como principal objetivo a análise da produção do conhecimento científico dos periódicos nacionais brasileiros de turismo quanto a publicações acerca do tema megaeventos, entre os anos de 2010 e 2015, por meio de um estudo bibliométrico. Compreender o quanto os estudiosos estão disseminando os dados de suas pesquisas nesses canais de divulgação científica se faz importante pela atual conjuntura do Brasil como país sede de megaeventos. Dentre os 1.760 artigos publicados no período pesquisado, identificaram-se 12 artigos sobre megaeventos, dos quais nove abordavam megaeventos esportivos, um megaevento musical, outro sobre estratégia turística e um sobre turismo de megaeventos. Sendo assim, foi possível compreender a diversidade de estudos sobre megaeventos e como suas temáticas podem contribuir para o turismo.
Aims/Hypothesis. The role of microRNAs (miRNAs) in type 1 diabetes (T1D) pathogenesis and progression has been described but remains elusive. Objectives. To evaluate the potential biological involvement of miRNA expression in the immune response and beta cell function in T1D. Methods.We screened 377 serum miRNAs of 110 subjects divided into four groups: healthy individuals (control group) and patients at different stages of T1D progression, from the initial immunological manifestation presenting islet autoantibodies (AbP group) until partial and strong beta cell damage in the recent (recent T1D group) and long-term T1D, with 2 to 5 years of disease (T1D 2-5y group).Results. The results revealed 69 differentially expressed miRNAs (DEMs) in relation to controls. Several miRNAs were correlated with islet autoantibodies (IA2A, GADA, and Znt8A), age, and C-peptide levels, mainly from AbP, and recent T1D groups pointing these miRNAs as relevant to T1D pathogenesis and progression. Several miRNAs were related to metabolic derangements, inflammatory pathways, and several other autoimmune diseases. Pathway analysis of putative DEM targets revealed an enrichment in pathways related to metabolic syndrome, inflammatory response, apoptosis and insulin signaling pathways, metabolic derangements, and decreased immunomodulation. One of the miRNAs’ gene targets was DYRK2 (dual-specificity tyrosine-phosphorylation-regulated kinase 2), which is an autoantigen targeted by an antibody in T1D. ROC curve analysis showed hsa-miR-16 and hsa-miR-200a-3p with AUCs greater than for glucose levels, with discriminating power for T1D prediction greater than glucose levels. Conclusions/Interpretation. Our data suggests a potential influence of DEMs on disease progression from the initial autoimmune lesion up to severe beta cell dysfunction and the role of miRNAs hsa-miR-16 and hsa-miR-200a-3p as biomarkers of T1D progression.
Background: The Sinovac SARS-CoV-2 inactivated vaccine (CoronaVac) has been demonstrated to be safe, well tolerated, and efficacious in preventing mild and severe Covid-19. Although different studies have demonstrated its short-term immunogenicity, long-term cellular and humoral response evaluations are still lacking. Methods: Cellular and humoral responses were assessed after enrollment of volunteers in the PROFISCOV phase 3 double-blind, randomized, placebo-controlled clinical trial to evaluate CoronaVac. Assays were performed using flow cytometry to evaluate cellular immune response and an antigen binding electrochemiluminescence assay to detect antigen-specific antibodies to the virus. Results: Fifty-three volunteers were selected for long term assessment of their SARS-CoV-2-specific immune responses. CD4+ T cell responses (including circulating follicular helper (cTfh, CD45RA- CXCR5+) expressing CD40L, as well as non-cTfh cells expressing CXCR3) were observed early upon the first vaccine dose, increased after the second dose, remaining stable for 6-months. Memory CD4+ T cells were detected in almost all vaccinees, the majority being central memory T cells. IgG levels against Wuhan/WH04/2020 N, S and receptor binding domain (RBD) antigens and the variants of concern (VOCs, including B.1.1.7/Alpha, B.1.351/Beta and P.1/Gamma) S and RBD antigens peaked 14 days after the second vaccine shot, and were mostly stable for a 1-year period. Conclusions: CoronaVac two-doses regimen is able to induce a potent and durable SARS-CoV-2 specific cellular response. The cellular reaction is part of a coordinated immune response that includes high levels of specific IgG levels against parental and SARS-CoV-2 VOC strains, still detected after one year. Funding: Fundacao Butantan, Instituto Butantan and Sao Paulo Research Foundation (FAPESP) (grants 2020/10127-1 and 2020/06409-1). This work has also been supported by NIH contract 75N93019C00065 (A.S, D.W). PATH facilitated reagent donations for this work with support by the Bill & Melinda Gates Foundation (INV-021239). Under the grant conditions of the foundation, a Creative Commons Attribution 4.0 generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission.
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