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猴痘自组装纳米颗粒候选疫苗的制备及免疫应答特征研究

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免疫学杂志 2024年第1期40卷 96-103页

作者：谭凌云王慧杨晓岚汪芳洲李燕罗德炎谷宏婧安徽医科大学基础医学院合肥230032 军事科学院军事医学研究院微生物流行病研究所病原微生物生物安全全国重点实验室北京100071

目的本研究旨在制备自组装纳米颗粒猴痘候选疫苗并研究其免疫应答特征,为其疫苗设计提供可参考的试验数据。方法利用原核系统表达纯化抗原蛋白A29L-SpyTag和骨架蛋白Mi3-SpyCatcher,化学组装制备纳米颗粒A29L-Mi3,皮下免疫小鼠,通过EL... 详细信息

目的本研究旨在制备自组装纳米颗粒猴痘候选疫苗并研究其免疫应答特征,为其疫苗设计提供可参考的试验数据。方法利用原核系统表达纯化抗原蛋白A29L-SpyTag和骨架蛋白Mi3-SpyCatcher,化学组装制备纳米颗粒A29L-Mi3,皮下免疫小鼠,通过ELISA测定抗体效价、空斑试验测定抗体中和、流式细胞术测定淋巴细胞分泌细胞因子情况,并描述其免疫应答特征。结果成功制备A29L-Mi3纳米颗粒,颗粒呈中空笼状均匀分布,其粒径平均为(29±0.19) nm。A29L-Mi3纳米颗粒候选疫苗联合SP01佐剂后,中和抗体效价强于A29L蛋白候选疫苗,且A29L-Mi3纳米颗粒候选疫苗免疫2次即能够获得免疫3次相近滴度的中和抗体。A29L-Mi3纳米颗粒候选疫苗激活的小鼠T淋巴细胞免疫应答水平高于A29L蛋白候选疫苗。结论成功体外组装制备出结构均一的A29L-Mi3蛋白纳米颗粒,具有较强的免疫原性,联合SP01佐剂后中和能力提高,为免疫程序的优化提供参考数据。细胞免疫应答水平均高于单独的A29L蛋白,为猴痘疫苗的设计与研发提供借鉴。

关键词：猴痘抗原A29L 自组装纳米颗粒疫苗体液免疫细胞免疫

An updated RBD-Fc fusion vaccine booster increases neutralization of SARS-CoV-2 Omicron variants

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Signal Transduction and Targeted Therapy 2022年第10期7卷 3652-3654页

作者： Deyan Luo Xiaolan Yang Tao Li Nianzhi Ning Song Jin Zhuangzhuang Shi hongjing gu Deyu Li Yuwei Gao Hui Wang State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyBeijing 100071China Key Laboratory of Jilin Province for Zoonosis Prevention and Control Veterinary Research InstituteChinese Academy of Agricultural SciencesChangchun 130021China

Dear Editor,Coronavirus disease 2019(COVID-19)is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),which is a novel subset of *** this day,the number of confirmed cases is over 500 million with more than 6 million deaths ***-2 keeps on evolving into different variants,including Alpha,Beta,Gamma,Delta,and Omicron.

关键词： acute respiratory vaccine

Transient acquisition of cross-species infectivity during the evolution of SARS-CoV-2

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National Science Review 2021年第11期8卷 85-87页

作者： Qi Chen Xing-Yao Huang Meng-Xu Sun Rui-Ting Li hongjing gu Ying Tian Rong-Rong Zhang Dan Luo Chao Zhou Yifei Zhang Tianshu Cao Na-Na Zhang Yong-Qiang Deng Xiao-Feng Li Cheng-Feng Qin State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyAMMS Research Unit of Discovery and Tracing of Natural Focus Diseases Chinese Academy of Medical Sciences

Since the coronavirus disease 2019(COVID-19) pandemic began,its causative agent,severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),has spread *** the global transmission of SARS-CoV-2,mutations in the viral ...

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Transcutaneous immunization using a dissolving microneedle array protects against staphylococcal enterotoxin B intoxication

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Transcutaneous immunization using a dissolving microneedle a...

第十三届全国免疫学学术大会

作者： Siqi Liu hongjing gu Shaogeng Zhang Xiliang Wang Penghui Yang Beijing 302 Hospital State Key Laboratory of Pathogens and Biosecurity Beijing Institute of Microbiology and Epidemiology

Staphylococcal enterotoxin B(SEB), which is produced by the Staphylococcus aureus bacterium, causes food poisoning and profound toxic shock ***, no approved vaccine or specific drug is available to treat SEB *** this study, we fabricated dissolving microneedles(MNs) loaded with recombinant SEB(rSEB) protein and evaluated its characteristics including dissolution profile, protein particle size, insertion depth, antigen retention time in vivo, and skin *** results showed that rSEB protein-loaded dissolving MNs made of chondroitin sulfate(2%) and trehalose(0.8%) could easily penetrate into the mouse skin in vivo within 5 *** rSEB particle size was unchanged before and after MN *** skin penetration depth of the MNs was 260μ***, the MNs also significantly extended the antigen retention time in *** addition, rSEB protein-loaded dissolving MNs triggered slight erythema at the beginning of administration, but this erythema disappeared within several *** importantly, we investigated whether rSEB protein-loaded dissolving MNs could induce robust immune responses that conferred protection against a lethal SEB *** challenge studies revealed that full-dose MN immunization induced a high level of antibody response, conferring 100% protection against a lethal SEB toxin challenge, but there was only a 60% survival rate in mice observed in the 1/2 dose MN(dose sparing)*** also determined the tissue pathological alterations of the immunized *** together, our dissolving MNs may present a promising transcutaneous immunization strategy for treating SEB intoxication.

关键词： dissolving microneedle transcutaneous immunization rSEB

Influenza virus vaccine expressing fusion and attachment protein epitopes of respiratory syncytial virus induces protective antibodies

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Influenza virus vaccine expressing fusion and attachment pro...

第十二届全国免疫学学术大会

作者： Wang Xiliang gu hongjing Wang Keyu Zhou Shanshan Penghui Yang Beijing Institute of Microbiology and Epidemiology State Key Laboratory of Pathogen and Biosecurity Beijing 302 Hospital

Respiratory syncytial virus(RSV) is an important viral pathogen that causes life-threatening respiratory infections in both infants and the elderly;no vaccines are at present *** this report,we examined the use of influenza virus as a vehicle for production of an experimental RSV *** used reverse genetics to generate a recombinant influenza A virus with epitopes from the RSV fusion(F) and attachment(G) proteins in the cold-adapted influenza virus NA *** of RSV F+G epitope proteins was confirmed by Western blotting,and no changes in viral morphology were evident following examination by electron *** rat immunized intranasally with rFlu/RSV/F+G showed viral-specific antibody responses against both influenza and *** IgG,IgG1,IgG2 a and IgA were measured in mice immunized with rFlu/RSV/F+G,revealing robust cellular and mucosal immune ***,we found that rFlu/RSV/F+G conferred protection against subsequent influenza and RSV challenges,showing significant decreases in viral replication and obvious attenuation of histopathological changes associated with viral *** findings suggest that rFlu/RSV/F+G is a promising vaccine candidate,which should be further assessed using primate models.

关键词： RSV fusion protein F and attachment(G) proteins Cold-adapted influenza virus

Angiotensin-converting enzyme 2(ACE2) mediates influenza H7N9 virus-induced acute lung injury

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Angiotensin-converting enzyme 2(ACE2) mediates influenza H7N...

第十届全国免疫学学术大会

作者： Penghui Yang hongjing gu Chengcai Lai Shaogeng Zhang Xiliang Wang Beijing302 Hospital State Key Laboratory of Pathogens and Biosecurity Beijing Institute of Microbiology and Epidemiology

Since 2013,the emergence of an avian-origin influenza A(H7N9)virus has raised concern in *** most infections resulted in respiratory illness,some severe cases resulted in acute respiratory distress syndrome(ARDS),which is a severe form of acute lung injury(ALI)that further contributes to *** date,no effective drugs that improve the clinical outcome of influenza A(H7N9)virus-infected patients have been ***-converting

关键词： H7N9 influenza ACE2 lung injury

Basic fibroblast growth factor protects against influenza A virus-induced acute lung injury by recruiting neutrophils

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Journal of Molecular Cell Biology 2018年第6期10卷 573-585页

作者： Keyu Wang Chengcai Lai Tieling Li Cheng Wang Wei Wang Bing Ni Changqing Bai Shaogeng Zhang Lina Han hongjing gu Zhongpeng Zhao Yueqiang Duan Xiaolan Yang Li Xing Lingna Zhao Shanshan Zhou Min Xia Chengyu Jiang Xiliang Wang Penghui Yang State Key Laboratory of Pathogens and Biosecurity Beijing Institute of Microbiology and EpidemiologyBeijing 100071China Chinese PLA General Hospital Beijing 100853China State Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical SciencesBeijing 100005China Institute of Immunology Third Military Medical UniversityChongqing 400038China Beijing 307 Hospital of PLA Affiliated with the Chinese Academy of Medical Sciences Beijing 100070China Beijing 302 Hospital of PLA Beijing 100039China

Influenza virus (IAV)infection is a major cause of severe respiratory illness that affects almost every country in the *** infections result in respiratory illness and even acute lung injury and death,but the underlying mechanisms responsible for IAV pathogenesis have not yet been fully *** this study,the basic fibroblast growth factor 2 (FGF2)level was markedly increased in H1N1 virus-infected humans and ***2,which is predominately derived from epithelial cells,recruits and activates neutrophils via the FGFR2-PI3K-AKT-NFKB signaling ***2 depletion or knockout exacerbated influenzaassociated disease by impairing neutrophil recruitment and *** importantly,administration of the recombinant FGF2 protein significantly aUeviated the severity of IAV-induced lung injury and promoted the survival of IAV-infected *** on the results from experiments in which neutrophils were depleted and adoptively transferred,FGF2 protected mice against IAV , infection by recruiting ***,FGF2 plays a critical role in preventing IAV-induced lung injury,and FGF2 is a promising potential therapeutic target during IAV infection.

关键词： influenza H1N1 virus recombinant FGF2 protein neutrophil recruitment FGFR2-PI3K-AKT-NFκB signaling therapeutic target

Influenza virus vaccine expressing fusion and attachment protein epitopes of respiratory syncytial virus induces protective antibodies in vivo

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Influenza virus vaccine expressing fusion and attachment pro...

第九届全国免疫学学术大会

作者： Penghui Yang Chengrong Bian Yueqiang Duan hongjing gu Shaogeng Zhang Xiliang Wang Beijing Institute of Microbiology and Epidemiology State Key Laboratory of Pathogen and Biosecurity Beijing302 Hospital

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Immunization with a live attenuated H7N9 influenza vaccine protects mice against lethal challenge

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Immunization with a live attenuated H7N9 influenza vaccine p...

第十届全国免疫学学术大会

作者： Yueqiang Duan Penghui Yang Xiaolan Yang Zhongpeng Zhao hongjing gu Xiliang Wang Beijing Institute of Microbiology and Epidemiology 302 hospitial

The emergence of severe cases of human influenza A(H7N9) viral infection in China in the spring of 2003 resulted in a global effort to rapidly develop an effective candidate vaccine. In this report, using reverse genetic technology, we generated a cold-adapted(ca), live attenuated monovalent reassortant influenza H7N9 virus(Ah01/AA ca) that contained hemagglutinin(HA) and neuraminidase(NA) genes from a 2013 pandemic A H7N9 isolate, A/Anhui/01/2013 virus(Ah01/H7N9);the remaining six internal gene segments came from the cold-adapted influenza H2N2 A/Ann Arbor/6/60 virus(AA virus). Ah01/AA ca exhibited phenotypes of temperature sensitivity(ts), ca, and attenuation(att). Intranasal immunization of female BALB/c mice with Ah01/AA ca twice at a 2-week interval induced robust humoral, mucosal, and cellmediated immune responses in a dose-dependent manner. Furthermore, the candidate Ah01/AA ca virus was immunogenic and offered partial or complete protection of mice against a lethal challenge by the live 2013 influenza A H7N9(A/Anhui/01/2013). Protection was demonstrated by the inhibition of viral replication and the attenuation of histopathological changes in the challenged mouse lung. Taken together, these data support the evaluation of this Ah01/AA ca candidate vaccine for human use in clinical trials.

关键词： H7N9 live attenuated vaccine cold-adapted