Human pDCs Are Superior to cDC2s in Attracting Cytolytic Lymphocytes in Melanoma Patients Receiving DC Vaccination

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Immunogenicity,effectiveness and safety of COVID-19 vaccine in older adults living in nursing homes: A real-life study

IntroductionBNT162b2 (BioNTech and Pfizer) is a nucleoside-modified mRNA vaccine that provides protection against SARS-CoV-2 infection and is generally well tolerated. However, data about its efficacy, immunogenicity and safety in people of old age or with underlying chronic conditions are scarce.PurposeTo describe BNT162b2 (BioNTech and Pfizer) COVID-19 vaccine immunogenicity, effectiveness and reactogenicity after complete vaccination (two doses), and immunogenicity and reactogenicity after one booster, in elders residing in nursing homes (NH) and healthy NH workers in real-life conditions.MethodsObservational, ambispective, multicenter study. Older adults and health workers were recruited from three nursing homes of a private hospital corporation located in three Spanish cities. The primary vaccination was carried out between January and March 2021. The follow-up was 13 months. Humoral immunity, adverse events, SARS-CoV-2 infections, hospitalizations and deaths were evaluated. Cellular immunity was assessed in a participant subset.ResultsA total of 181 residents (mean age 84.1 years; 89.9% females, Charlson index ≥2: 45%) and 148 members of staff (mean age 45.2 years; 70.2% females) were surveyed (n:329). After primary vaccination of 327 participants, vaccine response in both groups was similar; ≈70% of participants, regardless of the group, had an antibody titer above the cut-off considered currently protective (260 BAU/ml). This proportion increased significantly to ≈ 98% after the booster (p < 0.0001 in both groups). Immunogenicity was largely determined by a prior history of COVID-19 infection. Twenty residents and 3 workers were tested for cellular immunity. There was evidence of cellular immunity after primary vaccination and after booster. During the study, one resident was hospitalized for SARS-CoV-2. No SARS-CoV-2-related deaths were reported and most adverse events were mild.ConclusionsOur results suggest that the BNT162b2 mRNA COVID-19 vaccine is immunogenic, effective and safe in elderly NH residents with underlying chronic conditions.     

表达量高、血凝活性好的H3N2流感病毒血凝素（HA）蛋白疫苗的筛选研究

摘要 目的：筛选表达量高、血凝活性好的H3N2流感病毒血凝素（HA）重组蛋白。方法：以A/MINNESOTA/41/2019（H3N2）毒株的HA为基础,将HA胞外区N端融合GP67信号肽,C端融合三聚化基序,分别构建HA胞外区全长及近膜区截短2个氨基酸的HA重组杆状病毒,并构建相应的不含三聚化基序的HA重组杆状病毒;经昆虫细胞表达,Western blot鉴定,亲和层析纯化后分析重组蛋白的血凝效价及稳定性。结果：四种HA重组蛋白均获得有效表达,其中HA胞外区全长融合三聚化基序的重组蛋白（HA-T）表达水平最高,经Strep tag亲和层析获得高度纯化,产量高达30 mg/L,Ethylene glycolbis交联分析显示为稳定的HA三聚体形式,血凝活性分析显示HA-T的活性最高,血凝效价为29,动态光散射显示HA-T在4℃放置3个月性质稳定。结论：HA-T表达量高、稳定性好、血凝活性高且易于纯化,研究结果为流感重组蛋白疫苗的研发策略提供了参考。     

Structurally defined synthetic cancer vaccines: analysis of structure, glycosylation and recognition of cancer associated mucin, MUC-1 derived peptides

Translation of an immune response into therapy is probably the toughest task in designing vaccines for cancer due to the heterogeneity of the cell surface antigens which display tremendous variations in glycoforms. Consequently, a small segment (antigen) of the cancer-associated mucin, in spite of generating antigen-specific immune responses, may be limited in therapeutic value. It is important that the synthetic segment resembles the native cancer-associated mucin in both structure and conformation. Synthetic cancer associated mucin derived 16 amino acid peptide GVTSAPDTRAPAPGSTA and its partially glycosylated forms have demonstrated specific binding to two monoclonal antibodies, B27.29 and BCP8, raised against the native cancer associated mucin, MUC-1 and a MUC-1 derived synthetic peptide, respectively. In spite of the structural similarities at the core peptide level of both glycosylated and unglycosylated peptides, it appears that partial glycosylation does not inhibit and even slightly enhances binding to the MAb B27.29 indicating that the glycosylated synthetic peptide more closely resembles the native mucin epitope recognized by MAb B27.29. From molecular dynamic simulations using NMR derived distance constraints, both glycosylated and unglycosylated peptides have shown a type I turn involving the same amino acids in both glycosylated and unglycosylated peptides. The GalNAc attached to the threonine (T³) and serine (S⁴) in the 16 amino acid sequence has not imposed any conformational changes to the peptide backbone nor has offered severe steric resistance to the binding of either antibody to the glycopeptides as indicated by hapten inhibition studies. Nevertheless, all peptides have displayed glycosylation dependent specificities in binding to these antibodies, i.e. the glycosylated peptides demonstrated relative higher affinities to the native mucin antibody B27.29 while the unglycosylated peptide is more specific to the MAb BCP8. Immune responses generated by these synthetic glycopeptides are highly specific in recognizing the native cancer associated mucin.     

全球冠状病毒疫苗专利分析

冠状病毒是一类可感染人类和动物的RNA病毒,可引起严重急性呼吸综合征(SARS)和中东呼吸综合征(MERS)等严重疾病。新型冠状病毒是以前从未在人体中发现的冠状病毒新毒株,其人际传播迅速,引起了各国政府的高度重视并积极寻求疫苗防控对策。基于冠状病毒疫苗领域全景专利,在综合对比分析该领域的全部专利的发展趋势、主要国家和主要机构的专利产出的同时,重点揭示了其中的人用相关疫苗的发展与分布情况以及重点分析了人用疫苗产品的研发现状,以期为我国冠状病毒疫苗领域的科研工作者和管理决策者提供参考数据。     

利用细菌人工染色体技术构建整合F基因的重组MDV疫苗株*

目的:预防马立克氏病病毒(MDV)和新城疫病毒(NDV)混合感染鸡引起的疾病,构建表达NDV F蛋白的MDV疫苗株CVI988 BAC重组载体,并包装成重组病毒,为疫苗免疫提供更多的重组疫苗选择。方法:首先利用PCR扩增带有卡那霉素(Kanamycin,Kana)抗性基因片段的F基因,采用同源重组的方法将其整合到CVI988 BAC上,进一步诱导I-SceI表达敲除Kana基因而获得重组质粒CVI988 BAC-F。通过磷酸钙法转染鸡胚成纤维细胞获得重组病毒。结果:Western blot和间接免疫荧光实验证实重组病毒能够表达F蛋白。病毒生长曲线和蚀斑大小测定结果表明,F基因的插入不影响病毒的体外增殖。结论:利用BAC技术成功构建了整合F基因的重组MDV病毒CVI988 BAC-F,为MDV重组疫苗研发,防控NDV与MDV共感染奠定了基础。