作者: Klausen, Michael Schantz ; Persson, Gry ; Nicol, Mckayla J. ; Restori, Katherine H. ; Soerensen, Anders Bundgaard ; Emdrup, Julie Hincheli ; Kirimanjeswara, Girish ; Roenoe, Birgitte ; Schussek, Sophie ; Katkere, Bhuvana

The global SARS-CoV-2 pandemic caused significant social and economic disruption worldwide, despite highly effective vaccines being developed at an unprecedented speed.Because the first licensed vaccines target only single B-cell antigens, antigenic drift could lead to loss of efficacy against emerging SARSCoV-2 variants.Improving B-cell vaccines by including multiple T-cell epitopes could solve this problem.Here, we show that in silico predicted MHC class I/II ligands induce robust T-cell responses and protect against severe disease in genetically modified K18-hACE2/BL6 mice susceptible to SARS-CoV-2 infection.

2022-05-01·Journal of Immunological Methods4区 · 医学

In silico designed Staphylococcus aureus B-cell multi-epitope vaccine did not elicit antibodies against target antigens suggesting multi-domain approach

4区 · 医学

Article

作者: Ali, Amjad ; Ishaq, Zaara ; Lee, Bok Luel ; Rahman, Abdur ; Siddique, Abubakar ; Anwer, Farha ; Mao, Xinrui ; Ullah, Nimat ; Bae, Taeok ; Rahman, Moazur ; Jiang, TingTing ; Shah, Majid Ali

The vaccine development strategies have evolved from using an entire organism as an immunogen to a single antigen and further towards an epitope. Since an epitope is a relatively tiny and immunologically relevant part of an antigen, it has the potential to stimulate more robust and specific immune responses while causing minimal adverse effects. As a result, the recent focus of vaccine development has been to develop multi-epitope vaccines that can target multiple virulence mechanisms. Accordingly, we designed multi-epitope vaccine candidates B (multi-B-cell epitope immunogen) and CTB-B (an adjuvant - cholera toxin subunit B (CTB) - attached to immunogen B) against S. aureus by employing immunoinformatics approaches. The designed vaccines are composed of B-cell epitope segments (20-mer) of the eight well-characterized S. aureus virulence factors, namely ClfB, FnbpA, Hla, IsdA, IsdB, LukE, SdrD, and SdrE connected in series. The designed vaccines were expressed, purified, and administered to C57BL/6 mice with Freund adjuvant to evaluate the immunogenicity and protective efficacy. The results revealed that the immunized mice showed high IgG titers for the immunogen, and the antibody titers increased significantly following the second immunization. However, the generated antibodies did not protect the mice from infection. The interaction of anti-B antibodies with source virulence factors showed that the generated antibodies have no binding affinity with any of the corresponding virulence factors. Our results demonstrate the limitation of the in silico designed B-cell multi-epitope vaccine and suggest that a protein domain carrying both linear and conformational B-cell epitopes might be a better choice for developing an effective multi-epitope vaccine against S. aureus.

2022-02-26·Cureus

Systemic Lupus Erythematosus-Associated Serositis Managed With Intravenous Belimumab: A Case Report

作者: Alahari, Lakshmi ; Chamarti, Karthik ; Pillarisetty, Leela ; Ammu, Anusha ; Mukkera, Srikanth ; Vadlapatla, Rajeev K ; Vulasala, Sai Swarupa ; Mukkera, Akshathh ; Mannem, Maneesh

Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple organ systems. Due to the heterogeneity of its presentation, it is challenging for clinicians to diagnose and manage the symptoms. SLE has a wide range of presentations from mild to severe and involves various organ systems like mucocutaneous, musculoskeletal, cardiopulmonary, renal, gastrointestinal, and central nervous system. Various novel treatment modalities are being used based on clinical presentation. Prednisone and methylprednisolone are commonly used as needed for acute flares of SLE. Some patients may need a low dose of oral prednisone to keep their SLE under control, which carries a risk of coronary artery disease (CAD) and many other metabolic side effects of steroids. Other long-term medications that are commonly used include hydroxychloroquine, methotrexate, azathioprine, mycophenolate, cyclosporine, and cyclophosphamide. Intravenous cyclophosphamide is used only in severe lupus with renal, pulmonary, or CNS involvement. Rituximab is a human monoclonal B-cell cluster of differentiation (CD)20 receptor antibody used for severe SLE not responding with other medications. Other newer medications are belimumab and anifrolumab. Anifrolumab is a fully human monoclonal antibody that binds to subunit 1 of the type I interferon receptor. We present a case of a 25-year-old female with a chronic history of SLE presented to the outpatient clinic with abdominal distension that needed frequent abdominal paracenteses. She was using hydroxychloroquine, mycophenolate mofetil, and prednisone, but her symptoms were not adequately controlled. After we started the patient on monthly intravenous belimumab, her symptoms and the frequency of visits for paracentesis gradually reduced. B-cells are known to play an essential role in the pathogenesis of SLE, and the use of belimumab, an anti-BLys (B-lymphocyte stimulator) human monoclonal antibody that inhibits B-cell growth, can play a significant role in the management of SLE associated chronic serositis.

项与 TeloB-VAX 相关的新闻（医药）

2022-05-27

·生物探索

【探报24H】传奇CAR-T疗法欧盟获批；首个斑秃克星！欧盟CHMP推荐批准Olumiant

导语：传奇生物CAR-T疗法在欧盟获批上市；首个斑秃克星！欧盟CHMP推荐批准Olumiant；恒瑞医药双重机制降糖药申报上市......生物探索与您一同关注“药”闻，探索生物科技的价值！01传奇生物CAR-T疗法在欧盟获批上市5月26日，传奇生物宣布欧盟委员会已授予CARVYKTI®（西达基奥仑赛，英文通用名Ciltacabtagene Autoleucel，简称 Cilta-cel）附条件上市许可，用于治疗既往接受过至少三种治疗，包括免疫调节药物、蛋白酶体抑制剂和抗 CD38 抗体，并且末次治疗出现疾病进展的复发或难治性多发性骨髓瘤（R/R MM）成人患者。西达基奥仑赛是一款BCMA靶向CAR-T细胞疗法，传奇生物与强生在2017年12 月达成了全球独家许可和合作协议，以开发和商业化 Cilta-cel。今年2月28日，西达基奥仑赛获 FDA 批准在美国上市，不仅是传奇生物的一大里程碑，也是国内创新药出海的重要里程碑；西达基奥仑赛再下一城，在欧盟也成功获批上市。02首个斑秃克星！欧盟CHMP推荐批准Olumiant近日，礼来与合作伙伴Incyte近日联合宣布，欧洲药品管理局（EMA）人用医药产品委员会（CHMP）已发布一份积极审查意见，推荐批准口服JAK抑制剂Olumiant（中文商品名：艾乐明；通用名：baricitinib，巴瑞替尼），用于治疗成人重度斑秃。03恒瑞医药双重机制降糖药申报上市5月26日，中国国家药品监督管理局药品审评中心官网最新公示，恒瑞医药在研新药恒格列净二甲双胍缓释片已递交上市申请并获得受理。公开资料显示，这是一款治疗2型糖尿病的复方缓释制剂，由钠-葡萄糖协同转运体2抑制剂恒格列净与二甲双胍组成。04亘喜生物将在ASCO公布双靶点CAR-T长期随访数据5月27日，亘喜生物科技集团宣布将以口头报告形式在2022美国临床肿瘤学会年会（ASCO 2022）上汇报旗下B细胞成熟抗原（B-cell maturation antigen, BCMA）/CD19双靶点CAR-T候选产品GC012F针对复发/难治性多发性骨髓瘤开展的一项多中心、由研究者发起的临床试验的最新临床数据。 GC012F是一款双靶点自体CAR-T疗法，通过同时靶向BCMA及CD19靶点进行治疗。该候选产品依托于公司专有的FasTCAR平台技术，具备“次日完成生产”的优势。2021年11月，GC012F被美国食品药品监督管理局授予孤儿药资格认定，用于治疗多发性骨髓瘤。目前正在中国开展多项IIT研究，以评估其治疗多发性骨髓瘤和B细胞霍奇金淋巴瘤的效果。05诺诚健华靶向CD19单抗在中国获批II期临床5月26日，诺诚健华宣布其引进的靶向CD19单抗药物Tafasitamab联合来那度胺已经获得中国国家药监局批准开展单臂、开放、多中心临床II期研究。研究旨在评价这项联合疗法治疗不适合自体干细胞移植条件的复发或难治性弥漫性大B细胞淋巴瘤成人患者的安全性和有效性。Tafasitamab是一款靶向CD19的Fc结构域优化的人源化单克隆抗体，最初由Xencor公司开发，包含Xencor公司独有的XmAb工程化Fc结构域，因此显著强化了抗体依赖性细胞介导的细胞毒作用和抗体依赖性细胞吞噬作用，通过细胞凋亡和免疫效应机制介导B细胞肿瘤的裂解。整理|露娜排版|露娜End 往期精选围观史无前例！这些地方将建“永久性方舱”传递出哪些重要信号？热文Nature：被忽视的野生动物传播，助力新冠病毒“失控”突变热文你的长寿密码就在饮食中！看科学如何定义长寿饮食热文“复必泰”临床试验再度被延！“争相竞技”的国产mRNA疫苗谁能突出重围？热文抑制病毒复制15393倍！火速走红的千金藤素是“新冠神药”还是“空头支票” 点击“阅读原文”，了解更多~

免疫疗法细胞疗法合作抗体基因疗法

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