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Efficacy of seasonal pandemic influenza hemagglutinin DnA vaccines delivered by electroporation against aseasonal h1n1 virus challenge in mice

第十一届全国化学生物学学术会议

作者： Yinghua Li Bing Zhu Center Laboratory Guangzhou Women and Children’s Medical CenterGuangzhou Medical University

As an effective antiviral agent,the clinical application of Arbidol is limited by the appearance of drug-resistant *** overcome the limitation of drug-resistant,the use of modified nanoparticles with biological to explore novel anti-influenza drugs is developing *** antiviral activity of Selenium nanoparticles（SenPs） has attracted increasing attention in the biomedical *** modified SenPs by Arbidol（Se@ARB） with superior antiviral properties on drug resistance were synthesized in current *** decoration of SenPs（Se@ARB） with less toxicity had obviously inhibited h1n1 ***@ARB interfered with h1n1 influenza virus to host cells by suppressing the activity of hemagglutinin（hA） and neuraminidase（nA）.Se@ARB could prevent h1n1 form infecting MDCK cells and block DnA fragmentation and chromatin ***,Se@ARB evidently inhibited the generation of reactive oxygen species（ROS）.In vivo experiments indicated that Se@ARB prevent lung injury in h1n1 infected mice through hematoxylin and eosin *** test of lung tissues present that DnA damage reached a high level but reduced substantially when treated with Se@*** assay revealed that activations of caspase-3,AKT and MAPK signaling pathways were restrained by Se@ARB *** results demonstrate that Se@ARB is a promising antiviral pharmaceutical candidate for h1n1 influenza.

关键词： Selenium nanoparticles Arbidol h1n1 influenza virus neuraminidase Apoptosis

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Science China(Life Sciences) 2011年第4期54卷 293-299页

作者： TAn Lei LU huiJun ZhAnG Dan WAnG KaiYan TIAn MingYao LIU CunXia LIU YanYu hU Bo JIn ningYi Genetic Engineering Laboratory of PLA Academy of Military Medical Sciences of PLA Changchun 130062 China College of Animal Science and Veterinary Medicine Jilin University Changchun 130062 China Agricultural College of Yanbian University Yanji 133400 China

Prophylactic DnA vaccines against the influenza virus are promising alternatives to conventional vaccines. In this study, we generated two candidate gene-based influenza vaccines encoding either the seasonal or pandemic hemagglutinin antigen （hA） from the strains A/new Caledonia/20/99 （hIn1）（pV1AS） and A/Califorrtia/04/2009 （h1n1）（pVEh1）, respectively. After verifying antigen expression, the immunogenicity of the vaccines delivered intramuscularly with electroporation was tested in a mouse model. Sera of immunized animals were tested in hemagglutination inhibition assays and by ELISA for the presence of hA-specific antibodies. hA-specific T-cells were also measured in IFn-γ ELISpot assays. The protective efficacy of the candidate influenza vaccines was evaluated by measuring mortality rates and body weight after a challenge with 100 LD50 of mouse-adapted A/new Caledonia/20/99 （h1n1）. Mice immunized with either one of the two vaccines showed significantly higher T cell and humoral immune responses （P〈0.05） than the pVAX1 control group. Additionally, the pV1A5 vaccine effec- tively protected the mice against a lethal homologous mouse-adapted virus challenge with a survival rate of 100% compared with a 40% survival rate in the pVEh1 vaccinated group （P〈0.05）. Our study indicates that the seasonal influenza DnA vac- cine completely protects against the homologous A/new Caledonia/20/99 virus （h1n1）, while the pandemic influenza DnA vaccine only partially protects against this virus.

关键词： seasonal influenza pandemic influenza hemagglutinin DnA vaccine electroporation h1n1 influenza virus

Evolution analysis of influenza A (h1n1) virus based on the Sequences of Swine influenza viruses

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Evolution analysis of Influenza A (H1N1) Virus based on the ...

houttuynia cordata polysaccharide alleviated intestinal injury and modulated intestinal microbiota in h1n1 virus infected mice

第二届全国微生物资源学术暨国家微生物资源平台运行服务研讨会

作者： Jiuru Zhao,Kou Zheng,han Xia,Zhong Zhang,Zhaojun Fan,Shuang Tang,Tianxian Li(State Key Laboratory of Virology,Wuhan Institute of Virology,Chinese Academy of Sciences,Wuhan 430071,China.)

Based on the data from nCBI and the genome sequence of swine influenza virus(A/Swine/hubei/01/2007(h1n1)),which was isolated from hubei province of China in 2007,we constructed swine influenza virus data sets of Chinese *** latest datasets contained 408 sequences of 51 swine *** A/CaliforniA/04/2009(h1n1;CA/04/09) as representative strain,we analyzed the evolutionary relationship between novel h1n1 human influenza viruses and swine influenza viruses from Chinese *** highest similarity of all 8 genes between the CA/04/09 and Chinese mainland swine influenza virus was 91%-96%,and the evolutionary distances between them were relatively far(0.10787-0.02965;average:0.05743).The result showed that none of the viral genes in the gene pool of swine population in Chinese mainland was closed to those of novel h1n1 human influenza viruses.

关键词： h1n1 influenza virus Swine influenza virus Blast Evolution analysis

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Chinese Journal of natural Medicines 2019年第3期17卷 187-197页

作者： ChEn Mei-Yu LI hong LU Xiao-Xiao LInG Li-Jun WEnG hong-Bo SUn Wei ChEn Dao-Feng ZhAnG Yun-Yi Department of Pharmacology School of Pharmacy Fudan University Department of Pharmacognosy School of Pharmacy Fudan University

houttuynia cordata polysaccharide(hCP) is extracted from houttuynia cordata, a key traditional Chinese medicine. The study was to investigate the effects of hCP on intestinal barrier and microbiota in h1n1 virus infected mice. Mice were infected with h1n1 virus and orally administrated hCP at a dosage of 40 mg×kg^(–1)×d^(–1). h1n1 infection caused pulmonary and intestinal injury and gut microbiota imbalance. hCP significantly suppressed the expression of hypoxia inducible factor-1α and decreased mucosubstances in goblet cells, but restored the level of zonula occludens-1 in intestine. hCP also reversed the composition change of intestinal microbiota caused by h1n1 infection, with significantly reduced relative abundances of Vibrio and Bacillus, the pathogenic bacterial genera. Furthermore, hCP rebalanced the gut microbiota and restored the intestinal homeostasis to some degree. The inhibition of inflammation was associated with the reduced level of Toll-like receptors and interleukin-1β in intestine, as well as the increased production of interleukin-10. Oral administration of hCP alleviated lung injury and intestinal dysfunction caused by h1n1 infection. hCP may gain systemic treatment by local acting on intestine and microbiota. This study proved the high-value application of hCP.

关键词： h1n1 influenza virus houttuynia cordata Inflammation Intestinal Barrier Microbiota Polysaccharide

The role of RIP3 in the induction of influenza viral antigen specific CD8+T cell responses in C57BL/6 mice upon h1n1influenza virus infection

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The role of RIP3 in the induction of influenza viral antigen...

Interferon as a Mucosal Adjuvant for an influenza Vaccine in Pigs

第十四届全国免疫学学术大会

作者： Boyin Qin Chao Wang Lixiang Chen Yang Liu Xiaonan Ren Bin Wu Shun Li Xiaohui Zhou Shanghai public health clinical center

Objective:The purpose of this study was to explore whether RIP3 is involved in the induction and function of antigen-specific CD8T cells and memory CD8T cells in mice infected with influenza A virus ***:RIP3 and WT mice were infected through intranasal with influenza A h1 n1 PR8 virus(0.5 x LD50),*** spleen and peripheral blood of mice were dissected and collected in the post-infection effect stage(7 days after infection),memory formation stage β7 days after infection) and memory response stage β days after reinfection).The number and proportion of virus-specific effector CD8+T cells were detected by flow cytometry,and the expression of cytokines IFn-γ,TnF-α,IL-2 and GranzymeB were detected by flow *** the same time,the expression of immune checkpoint molecules PD-1,LAG-3,Tim-3 and CTLA-4 of CD8CD44 T cell subsets in mouse spleen was *** proportion of CD8T cells differentiated into TCM and TEM/TEff in the memory response phase was also ***:In the effect stage,there were few influenza antigen-specific CD8T cells in the spleen of RIP3 infected mice,and the expression levels of effector cytokines IFn-γ,TnF-α,IL-2 and GranzymeB on CD8+T cells were significantly lower than those in WT *** the same time,the immune checkpoint molecules LAG-3 and Tim-3 expressed by CD8+T cells in RIP3 infected group were significantly lower than those in WT *** the memory stage,the number of antigen-specific CD8T cells in peripheral blood of RIP3 mice was significantly lower than that of WT *** the stage of memory response,the number of antigen-specific CD8T cells produced by RIP3 mice and the ability of CD8T cells to secrete IFn-y were significantly lower than those of WT *** the phenotypes of activated memory CD8+T cells,the proportion of TEM in WT mice was significantly higher than that in RIP3 mice,while the proportion of TCM in WT mice was significantly lower than that in RIP3 ***:This study suggests t

关键词： Receptor-interacting protein 3(RIP3) h1n1 influenza virus antigen specific CD8+T cells

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Virologica Sinica 2019年第3期34卷 324-333页

作者： Lirong Liu Wenhui Fan he Zhang Shuang Zhang Liang Cui Meng Wang Xiaoyuan Bai Wenxian Yang Lei Sun Limin Yang Wenjun Liu Jing Li CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Interferon, a natural protein that is produced by a variety of cells during viral infection, activates the transcription of multiple functional genes in cells, regulates synergy among various signaling pathways, and mediates many biological functions such as antiviral activity, immune regulation, and cell growth. however, clinical research on interferon in livestock is lacking. In this study, recombinant porcine interferon(PoIFna) was used as an adjuvant, in combination with inactivated influenza virus, to vaccinate 6-week-old pigs via nasal infusion. The transcription of target genes was then monitored and the functions of PoIFna were determined with respect to the activation of mucosal immunity. We found that a combination of low-dose PoIFna and inactivated influenza virus could significantly up-regulate the expression of immunoregulatory cytokines such as IL-2, IL-18, IFn-c, IL-6, and IL-10 by real-time PCR, suggesting the induction of a strong mucosal innate immune response after administration. In addition, low-dose PoIFna can significant enhancing the transcription of genes encoding homing factors including CCR9 and CCR10(P \ 0.001), thereby resulting in the induction of higher levels of hA-specific antibodies(P \ 0.05), which can be determined by ELISA and IFA. Post-immunization challenges with h1 n1 virus demonstrated that PoIFna, combined with inactivated influenza virus, could alleviate clinical signs in pigs during the early stages of viral infection. These studies reveal low-dose PoIFna as a potential mucosal adjuvant for influenza virus in pigs.

关键词： Porcine interferon a(PoIFna) h1n1 influenza virus Intranasal administration Cytokines

Viral shedding in Chinese young adults with mild 2009 h1n： influenza

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Chinese Medical Journal 2011年第10期124卷 1576-1579页

作者： JIA ning GAO Yan SUO Ji-jiang XIE Li-jun YAn Zhong-qiang XInG Yu-bin hE Lei LIU Yun-xi Department of nosocomial Infection and Disease Control People's Liberation Army General Hospital Beijing 100853. China Department of Police Research People's Liberation Army General Hospital Beijing 100853. China Department of hepatobiliary Surgery People's Liberation Army General Hospital Beijing 100853. China

Background The duration of viral shedding and the transmission of 2009 h1n1 influenza among individuals, especially among the younger population with mild illness, are not well understood now. The aim of this study was to determine the viral shedding of the young adult patients with mild 2009 h1n1 influenza in *** From September 2009 to January 2010, the clinical data and serial nasopharyngeal swabs of 67 patients with 2009 h1n1 influenza and 37 patients with seasonal influenza aged from 18 years to 35 years were collected. The nasopharyngeal swab samples were detected by real time RT-PCR to determine the viral shedding. All the patients did not receive the antiviral therapy but Chinese medicine for *** Among the patients with h1n1 virus infection, 82.1% （55/67） patients presented with fever symptom, while more patients with high fever （≥39℃） were found in seasonal influenza patients （P〈0.05）. For the h1n1 patients, the median interval between the symptom onset and the undetectable RnA was six days （4-10 days）. But viral shedding was still found in 31.3% patients after 7 days following illness onset. The median interval between disappearance of fever and an undetectable viral RnA level was three days （2-8 days）, and 17.9% patients were found to be viral shedding 6 days later after normalization of body temperature. For the seasonal influenza patients, 94.6% patients were detected out viral RnA within 7 days. The median interval of seasonal influenza between the symptom onset and the undetectable RnA was four days （3-8 days）. The median interval between disappearance of fever and an undetectable viral RnA level was three days （2-6 days）.Conclusion It suggests that 7 days isolation period from the illness onset or 24 hours after the resolution of fever and respiratory symptoms are not long enough to cut off the transmission among Chinese young adults with mild illness

关键词： h1n1 influenza virus infection viral shedding