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Hepatitis B virus (HBV) is an ancient virus that has evolved unique strategies to persist as a chronic infection in humans. Here, I summarize the innate and adaptive features of the HBV-host interaction, and I discuss how different profiles of antiviral immunity cannot be predicted only on the basis of virological and clinical parameters.
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AIMS: Individuals with type 1 diabetes (T1D) do not appear to have an elevated risk of severe Coronavirus Disease 19 (COVID-19). Pre-existing immune reactivity to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in unexposed individuals may serve as a protective factor. Hence, our study was designed to evaluate the existence of T cells with reactivity against SARS-CoV-2 antigens in unexposed patients with T1D. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from SARS-CoV-2 unexposed patients with T1D and healthy control subjects. SARS-CoV-2 specific T cells were identified in PBMCs by ex-vivo interferon (IFN)γ-ELISpot and flow cytometric assays. The epitope specificity of T cells in T1D was inferred through T Cell Receptor sequencing and GLIPH2 clustering analysis. RESULTS: T1D patients unexposed to SARS-CoV-2 exhibited higher rates of virus-specific T cells than controls. The T cells primarily responded to peptides from the ORF7/8, ORF3a, and nucleocapsid proteins. Nucleocapsid peptides predominantly indicated a CD4+ response, whereas ORF3a and ORF7/8 peptides elicited both CD4+ and CD8+ responses. The GLIPH2 clustering analysis of TCRß sequences suggested that TCRß clusters, associated with the autoantigens proinsulin and Zinc transporter 8 (ZnT-8), might share specificity towards ORF7b and ORF3a viral epitopes. Notably, PBMCs from three T1D patients exhibited T cell reactivity against both ORF7b/ORF3a viral epitopes and proinsulin/ZnT-8 autoantigens. CONCLUSIONS: The increased frequency of SAR-CoV-2- reactive T cells in T1D patients might protect against severe COVID-19 and overt infections. These results emphasise the long-standing association between viral infections and T1D.
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COVID-19 , Diabetes Mellitus Tipo 1 , SARS-CoV-2 , Humanos , Diabetes Mellitus Tipo 1/imunologia , SARS-CoV-2/imunologia , COVID-19/imunologia , Masculino , Feminino , Adulto , Linfócitos T/imunologia , Pessoa de Meia-Idade , Estudos de Casos e Controles , Epitopos de Linfócito T/imunologia , Adulto JovemRESUMO
Heterologous Sinovac-CoronaVac booster(s) in 12-17-year-olds who had a moderate/severe reaction to Pfizer-BNT162b2 mRNA vaccine was found to safe with no serious adverse events reported. In those primed with 1 dose of Pfizer-BNT162b2 vaccine, subsequent boosters with 2 doses of Sinovac-CoronaVac vaccines achieved neutralizing antibody levels which were comparable to those who had received 2 doses of Pfizer-BNT162b2 vaccines followed by 1 dose of Sinovac-CoronaVac vaccination. Adolescents with 1 Pfizer-BNT162b2 followed by 2 Sinovac-CoronaVac vaccines developed T-cell responses against broad peptides including membrane, nucleoprotein 1 and 2 but levels were highest for Spike protein and lasted until day 150 post-vaccination.
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Vacina BNT162 , Vacinação , Vacinas de Produtos Inativados , Adolescente , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacina BNT162/efeitos adversos , Vacinação/efeitos adversos , Vacinas de Produtos Inativados/efeitos adversos , CriançaRESUMO
BACKGROUND: Hybrid immunity to SARS-CoV-2, resulting from both vaccination and natural infection, remains insufficiently understood in paediatric populations, despite increasing rates of breakthrough infections among vaccinated children. METHODS: We conducted a prospective longitudinal study to investigate the magnitude, specificity, and cytokine profile of antigen-specific T cell responses elicited by breakthrough SARS-CoV-2 infection in a cohort of mRNA-vaccinated children (n = 29) aged 5-11. This longitudinal analysis involved six distinct time points spanning a 16-month period post-vaccination, during which we analysed a total of 159 blood samples. All children who were followed for at least 12 months (n = 26) experienced a breakthrough infection. We conducted cytokine release assays using minimal blood samples, and we verified the cellular origin of these responses through intracellular cytokine staining. FINDINGS: After breakthrough infection, children who had received mRNA vaccines showed enhanced Th1 responses specific to Spike peptides. Additionally, their Spike-specific T cells exhibited a distinctive enrichment of CD4+ IFN-γ+IL10+ cells, a characteristic akin to adults with hybrid immunity. Importantly, vaccination did not impede the development of multi-specific T cell responses targeting Membrane, Nucleoprotein, and ORF3a/7/8 antigens. INTERPRETATION: Children, previously primed with a Spike-based mRNA vaccine and experiencing either symptomatic or asymptomatic breakthrough infection, retained the ability to enhance and diversify Th1/IL-10 antigen-specific T cell responses against multiple SARS-CoV-2 proteins. These findings mirror characteristics associated with hybrid cellular immunity in adults, known to confer resistance against severe COVID-19. FUNDING: This study was funded by the National Medical Research Council (NMRC) Singapore (COVID19RF-0019, MOH-000019, MOH-000535, OFLCG19May-0034 and MOH-OFYIRG19nov-0002).
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/virologia , SARS-CoV-2/imunologia , Criança , Estudos Longitudinais , Masculino , Feminino , Pré-Escolar , Citocinas/metabolismo , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Estudos Prospectivos , Vacinação , Vacinas de mRNA/imunologia , Linfócitos T/imunologia , Células Th1/imunologiaRESUMO
Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), the etiological agent of Coronavirus Diseases 2019 (COVID-19), triggers an adaptive immunity in the infected host that results in the production of virus-specific antibodies and T cells. Although kinetic and quantitative aspects of antibodies have been analyzed in large patient cohorts, similar information about SARS-CoV-2-specific T cells are scarce. We summarize the available knowledge of quantitative and temporal features of the SARS-CoV-2 T-cell response in this review. Currently, most of the data are derived only from the analysis of the circulatory compartment. Despite this limitation, early appearance, multi-specificity and functionality of SARS-CoV-2-specific T cells are associated with accelerated viral clearance and with protection from severe COVID-19.