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Combination therapy with oncolytic virus and T cells or mRNA vaccine amplifies antitumor effects

Signal Transduction and Targeted Therapy 2024年第6期9卷 2655-2668页

作者： Rao Fu Ruoyao Qi Hualong Xiong Xing Lei Yao Jiang Jinhang He Feng Chen Liang Zhang Dekui Qiu Yiyi Chen Meifeng Nie Xueran Guo Yuhe Zhu Jinlei Zhang Mingxi Yue Jiali Cao Guosong Wang yuqiong que Mujing Fang Yingbin Wang Yixin Chen Tong Cheng Shengxiang Ge Jun Zhang Quan Yuan Tianying Zhang Ningshao Xia State Key Laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine LaboratoryDepartment of Laboratory MedicineSchool of Public Health&School of Life SciencesXiamen UniversityXiamen 361102 FujianChina National Institute of Diagnostics and Vaccine Development in Infectious Diseases Xiamen 361102 FujianChina

Antitumor therapies based on adoptively transferred T cells or oncolytic viruses have made significant progress in recent years,but the limited efficiency of their infiltration into solid tumors makes it difficult to achieve desired antitumor effects when used *** this study,an oncolytic virus(rVSV-LCMVG)that is not prone to induce virus-neutralizing antibodies was designed and combined with adoptively transferred T *** transforming the immunosuppressive tumor microenvironment into an immunosensitive one,in B16 tumor-bearing mice,combination therapy showed superior antitumor effects than *** occurred whether the OV was administered intratumorally or *** therapy significantly increased cytokine and chemokine levels within tumors and recruited CD8^(+)T cells to the TME to trigger antitumor immune *** with adoptively transferred T cells and subsequent oncolytic virotherapy sensitizes refractory tumors by boosting T-cell recruitment,downregulating the expression of PD-1,and restoring effector T-cell *** offer a combination therapy with greater translational value,mRNA vaccines were introduced to induce tumor-specific T cells instead of adoptively transferred T *** combination of OVs and mRNA vaccine also displays a significant reduction in tumor burden and prolonged *** study proposed a rational combination therapy of OVs with adoptive T-cell transfer or mRNA vaccines encoding tumor-associated antigens,in terms of synergistic efficacy and mechanism.

关键词： transferred rational boosting

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Two antibodies show broad,synergistic neutralization against SARS-CoV-2 variants by inducing conformational change within the RBD

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Protein & Cell 2024年第2期15卷 121-134页

作者： Hui Sun Tingting Deng Yali Zhang Yanling Lin Yanan Jiang Yichao Jiang Yang Huang Shuo Song Lingyan Cui Tingting Li Hualong Xiong Miaolin Lan Liqin Liu Yu Li Qianjiao Fang Kunyu Yu Wenling Jiang Lizhi Zhou yuqiong que Tianying Zhang Quan Yuan Tong Cheng Zheng Zhang Hai Yu Jun Zhang Wenxin Luo Shaowei Li Qingbing Zheng Ying Gu Ningshao Xia State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China National Institute of Diagnostics and Vaccine Development in Infectious Diseases School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China State Key Laboratory of Vaccines for Infectious Diseases School of Public HealthSchool of Life SciencesXiamen UniversityXiamen 361102China Xiang An Biomedicine Laboratory Xiamen 361102China Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People's HospitalSchool of MedicineSouthem University of Science and TechnologyShenzhen 518112China The Second Affliated Hospital School of MedicineSouthern University of Science and TechnologyShenzhen 518112China Research Unit of Frontier Technology of Structural Vaccinology Chinese Academy of Medical SciencesXiamen 361102China

Continual evolution of the severe acute respiratory syndrome coronavirus(SARS-CoV-2)virus has allowed for its gradual evasion of neutralizing antibodies(nAbs)produced in response to natural infection or *** rapid nature of these changes has incited a need for the development of superior broad nAbs(bnAbs)and/or the rational design of an antibody cocktail that can protect against the mutated virus ***,we report two angiotensin-converting enzyme 2 competing nAbs—8H12 and 3E2—with synergistic neutralization but evaded by some Omicron ***-electron microscopy reveals the two nAbs synergistic neutralizing virus through a rigorous pairing permitted by rearrangement of the 472-489 loop in the receptor-binding domain to avoid steric *** antibodies based on these two nAbs tremendously extend the neutralizing breadth and restore neutralization against recent variants including currently dominant ***,these findings expand our understanding of the potential strategies for the neutralization of SARS-CoV-2 variants toward the design of broad-acting antibody therapeutics and vaccines.

关键词： SARS-CoV-2 broad neutralizing antibody rearrangement synergistic neutralization

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Varicella-zoster virus ORF7 interacts with ORF53 and plays a role in its trans-Golgi network localization

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Virologica Sinica 2017年第5期32卷 387-395页

作者： Wei Wang Wenkun Fu Dequan Pan Linli Cai Jianghui Ye Jian Liu Che Liu yuqiong que Ningshao Xia Hua Zhu Tong Cheng State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Institute of Diagnostics and Vaccine Development in Infectious Diseases School of Public Health Xiamen University Department of Microbiology Biochemistry and Molecular Genetics New Jersey Medical SchoolRutgers University

Varicella-zoster virus(VZV) is a neurotropic alphaherpesvirus that causes chickenpox and shingles. ORF7 is an important virulence determinant of VZV in both human skin and nerve tissues,however, its specific function and involved molecular mechanism in VZV pathogenesis remain largely elusive. Previous yeast two-hybrid studies on intraviral protein-protein interaction network in herpesviruses have revealed that VZV ORF7 may interact with ORF53, which is a virtually unstudied but essential viral protein. The aim of this study is to identify and characterize VZV ORF53, and to investigate its relationship with ORF7. For this purpose, we prepared monoclonal antibodies against ORF53 and, for the first time, characterized it as a ~40 k Da viral protein predominantly localizing to the trans-Golgi network of the infected host cell. Next, we further confirmed the interaction between ORF7 and ORF53 by co-immunoprecipitation and co-localization studies in both plasmid-transfected and VZV-infected cells. Moreover, interestingly, we found that ORF53 lost its trans-Golgi network localization and became dispersed in the cytoplasm of host cells infected with an ORF7-deleted recombinant VZV, and thus ORF7 seems to play a role in normal subcellular localization of ORF53. Collectively, these results suggested that ORF7 and ORF53 may function as a complex during infection, which may be implicated in VZV pathogenesis.

关键词： varicella-zoster virus(VZV) ORF7 ORF53 protein-protein interaction trans-Golgi network

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厦门市健康人群肠道病毒D68型血清流行病学调查

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病毒学报 2022年第2期38卷 341-347页

作者：林雨朱瑞吴圆圆徐龙发尹志超杨宏伟郑清炳阙玉琼叶江辉何水珍程通夏宁邵国家传染病诊断试剂与疫苗工程技术研究中心厦门大学公共卫生学院厦门大学生命科学学院厦门361102 厦门市疾病预防与控制中心厦门361021

肠道病毒D68型(Enterovirus D68,EV-D68)是一种可引起急性呼吸道感染并诱发中枢神经系统疾病的小RNA病毒。开展相关血清流行病学调查,有助于了解病毒在人群中的感染水平,为制定有效防控策略提供科学依据。本研究为了解厦门市EV-D68的流... 详细信息

肠道病毒D68型(Enterovirus D68,EV-D68)是一种可引起急性呼吸道感染并诱发中枢神经系统疾病的小RNA病毒。开展相关血清流行病学调查,有助于了解病毒在人群中的感染水平,为制定有效防控策略提供科学依据。本研究为了解厦门市EV-D68的流行概况与流行病学特征,采用分层随机抽样的方式收集了2016年厦门市健康人群血清标本共515份,应用基于酶联免疫斑点检测技术的中和试验(Enzyme-linked immunospot assay)检测针对EV-D68流行株的血清中和抗体滴度。结果显示,血清样本中EV-D68中和抗体的总体阳性率为81.9%,中和抗体的总体几何平均滴度(Geometric Mean Titer,GMT)为248.0。0.05);地理位置上,市区与郊区的EV-D68中和抗体阳性率没有显著差异(P=0.0986),市中心的中和抗体GMT略低于郊区(P=0.0069)。本研究表明,厦门市健康人群中EV-D68中和抗体阳性率和GMT随年龄增长呈上升趋势,年龄是影响EV-D68感染和流行的关键因素;并且,该地各年龄人群中存在EV-D68既往感染,幼龄儿童的抗体保护水平低,需要加强对易感人群的防控措施,防止出现暴发流行。

关键词：肠道病毒D68型(EV-D68) 血清流行病学中和抗体血清阳性率几何平均滴度

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水痘-带状疱疹病毒ORF43蛋白的单克隆抗体制备及初步研究

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病毒学报 2021年第6期37卷 1302-1309页

作者：翟兵可潘德全付文锟蔡雨泽王玮赵欢阙玉琼程通夏宁邵国家传染病诊断试剂与疫苗工程技术研究中心厦门大学生命科学学院厦门361102 分子疫苗学和分子诊断学国家重点实验室厦门大学公共卫生学院厦门361102

水痘-带状疱疹病毒(Varicella-zoster virus,VZV)是引起水痘和带状疱疹这两种临床表现不同病症的共同致病原,其基因组中ORF43是VZV在宿主细胞中复制的必需基因,但目前尚无针对VZV ORF43编码蛋白性质与功能的研究报道。本研究目的是制备... 详细信息

水痘-带状疱疹病毒(Varicella-zoster virus,VZV)是引起水痘和带状疱疹这两种临床表现不同病症的共同致病原,其基因组中ORF43是VZV在宿主细胞中复制的必需基因,但目前尚无针对VZV ORF43编码蛋白性质与功能的研究报道。本研究目的是制备抗VZV ORF43单克隆抗体,以初步研究该蛋白在细胞内的表达与分布情况。本研究构建了VZV ORF43蛋白的原核表达质粒并在大肠杆菌中进行了该蛋白的表达,纯化蛋白免疫小鼠后,使用杂交瘤技术及克隆化筛选,获得一株特异性强、反应性好的抗VZV ORF43单克隆抗体2D3。本研究使用该抗体鉴定出VZV ORF43蛋白在质粒转染细胞与病毒感染细胞中表达的分子量大小均约为70kD,但分别呈现出细胞质和细胞核的不同亚细胞定位。以上工作为后续进一步探究该蛋白在VZV感染与致病过程中的作用奠定了基础。

关键词：水痘-带状疱疹病毒(VZV) ORF43 单克隆抗体

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