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A novel live attenuated vaccine candidate protects chickens against subtype B avian metapneumovirus

Journal of Integrative Agriculture 2024年第5期23卷 1658-1670页

作者： Lingzhai Meng Mengmeng Yu Suyan Wang Yuntong Chen Yuanling Bao Peng Liu Xiaoyan Feng Tana He Ru Guo Tao Zhang Mingxue Hu Changjun Liu Xiaole Qi Kai Li Li Gao Yanping Zhang Hongyu Cui Yulong Gao Avian Immunosuppressive Diseases Division State Key Laboratory for Animal Disease Control and PreventionHarbin Veterinary Research InstituteChineseAcademy of Agricultural SciencesHarbin150069China Avian ImmunosuppressiveDiseases DivisionStateKey LaboratoryforAnimal Disease Cont National Poultry Laboratory Animal Resource Center Harbin 150069China

Avian metapneumovirus(aMPV) is a highly contagious pathogen that causes acute upper respiratory tract diseases in chickens and turkeys, resulting in serious economic losses. Subtype B aMPV has recently become the dominant epidemic strain in China. We developed an attenuated aMPV subtype B strain by serial passaging in Vero cells and evaluated its safety and efficacy as a vaccine candidate. The safety test showed that after the 30th passage, the LN16-A strain was fully attenuated, as clinical signs of infection and histological lesions were absent after inoculation.The LN16-A strain did not revert to a virulent strain after five serial passages in chickens. The genomic sequence of LN16-A differed from that of the parent wild-type LN16(wtLN16) strain and had nine amino acid mutations. In chickens, a single immunization with LN16-A induced robust humoral and cellular immune responses, including the abundant production of neutralizing antibodies, CD4^(+) T lymphocytes, and the Th1(IFN-γ) and Th2(IL-4 and IL-6)cytokines. We also confirmed that LN16-A provided 100% protection against subtype B aMPV and significantly reduced viral shedding and turbinate inflammation. Our findings suggest that the LN16-A strain is a promising live attenuated vaccine candidate that can prevent infection with subtype B aMPV.

关键词： avian metapneumovirus attenuated protection vaccine candidate chickens

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A new can didate vaccine for human brucellosis based on influenza viral vectors:a preliminary investigation for the development of an immunization schedule in a guinea pig model

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Infectious Diseases of Poverty 2021年第1期10卷 56-65页

作者： Dina Bugybayeva Zhailaubay Kydyrbayev Nadezhda Zinina Nurika Assanzhanova Bolat Yespembetov Yerken Kozhamkulov Kunsulu Zakarya Sholpan Ryskeldinova Kaissar Tabynov Research Institute for Biological Safety Problems 15 MomushulyGvardeyskiy 080409Kazakhstan Kazakh National Agrarian University 8 Abay AvenueAlmaty 050010Kazakhstan Research Institute of Cardiology and Internal Medicine 120 Aiteke biAlmaty 050000Kazakhstan.

Background:A new candidate vector vaccine against human brucellosis based on recombinant influenza viral vectors(rIVV)subtypes H5N1 expressing Brucella outer membrane protein(Omp)16,L7/L12,Omp19or Cu-Zn SOD proteins has been developed.This paper presents the results of the study of protection of the vaccine using on guinea pigs,including various options of administering,dose and frequency.Provided data of the novel vaccine candidate will contribute to its further movement into the preclinical stage study.Methods:General states of guinea pigs was assessed based on behavior and dynamics of a guinea pig weight-gain test.The effectiveness of the new anti-brucellosis vector vaccine was determined by studying its protective effect after conjunctival,intranasal and sublingual administration in doses 10^(5) EID50,10^(6) EID_(50) and 10^(7) EID_(50) during prime and boost vaccinations of animals,followed by challenge with a virulent strain of B.melitensis 16 M infection.For sake of comparison,the commercial ft melitensis Rev.1 vaccine was used as a control.The protective properties of vaccines were assessed by quantitation of Brucella colonization in organs and tissues of infected animals and compared to the control groups.Results:It was observed a gradual increase in body weight of guinea pigs after prime and booster immunization with the vacci ne using conjunctival,intra nasal and subli ngual routes of administration,as well as after using various doses of vaccine.The most optimal way of using the vaccine has been established:double intranasal immunization of guinea pigs at a dose of 10^(6) EID50, which provides 80%protection of guinea pigs from B.melitensis 16 M infection(Pvaccine candidate against brucellosis and developed its immunization protocol in guinea pig model.We believe that because of these studies,the proposed vaccine has achieved the best level of protectio

关键词： Human brucellosis Influenza viral vectors vaccine candidate Protection Guinea pigs Immunization route Vaccination dose

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Neospora caninum immune mapped protein 1(NcIMP1) is a novel vaccine candidate against neosporosis

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Frontiers of Agricultural Science and Engineering 2015年第1期2卷 66-72页

作者： Xia CUI Daoyu YANG Tao LEI Hui WANG Pan HAO Qun LIU Key Laboratory of Zoonosis of Ministry of Agriculture and National Animal Protozoa Laboratory College of Veterinary Medicine China Agricultural University

The Neospora caninum immune mapped protein 1(Nc IMP1) was identified as a membrane protein,and a previous study indicated that Nc IMP1 could be a promising vaccine candidate against neosporosis. In this study, the immune response and protection efficacy of Nc IMP1 were evaluated. The coding sequence of Nc IMP1 was inserted into the eukaryotic expression vector pc DNA3.1(+), resulting in the recombination plasmid pc DNAIMP1, which was used for the intramuscular immunization of BALB/c mice. After immunization, the immune response was evaluated using a lymphoproliferative assay and cytokine and antibody measurements. Quantification of the cerebral parasite burden of mice challenged with 2106 N. caninum was performed 14 days after the last immunization. The results showed that the mice immunized with pc DNA-IMP1 developed a high level of specific antibody responses against recombinant Nc IMP1,with a mixed Ig G1/Ig G2 a response and a predominance of Ig G2 a production. The cellular immune response was associated with the production of IFN-γ, IL-2, IL-4 and IL-10 cytokines. The experiment was terminated 30 days p.i.,and the cerebral parasite burden in each mouse was assessed by quantitative PCR. The parasite burden was significantly reduced in the pc DNA-IMP1-vaccinated mice. These data suggest that IMP1 is a promising vaccine candidate against neosporosis.

关键词： Neospora caninum immune mapped protein 1(IMP1) vaccine candidate BALB/c mice

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RR1 and RR2 gene deletion affects the immunogenicity of a live attenuated pseudorabies virus vaccine candidate in natural pig host

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Frontiers of Agricultural Science and Engineering 2016年第1期3卷 81-86页

作者： Shijun YAN He YAN Chaolin ZHANG Tongyan WANG Qingyuan YANG Zhe SUN Yan XIAO Feifei TAN Xiangdong LI Kegong TIAN National Research Center for Veterinary Medicine College of Animal Science and Veterinary Medicine Henan Agricultural University

As virulence-determining genes, RR1 and RR2 encode the small subunit and large subunit of viral ribonucleotide reductase(RR) in pseudorabies virus which have been extensively studied in mice. However,their role in pigs has not been adequately investigated. In this study, we deleted RR1 and RR2 genes based on a TK/g E/g I triple gene-deleted pseudorabies virus and tested its efficacy in pigs as a vaccine candidate. The rescued virus showed similar growth properties and plaque size in vitro as its parent strain. In an animal study, the virus could elicit humoral immune responses shown by generation of g B-specific antibodies and virus neutralizing antibodies.However, vaccination could not provide protection against virulent pseudorabies virus challenge since vaccinated pigs showed clinical pseudorabies-specific syndromes. The deficiency in protection may due to the generation of late and low levels of gB antibodies and virus neutralizing antibodies.

关键词： pseudorabies virus RR1 and RR2 ribonucleotide reductase vaccine candidate

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vaccine development for leptospirosis:A systematic review

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Asian Pacific Journal of Tropical Medicine 2023年第12期16卷 533-545页

作者： Yocyny Surendran Mahalingam Nandikha Syafinaz Amin-Nordin Sandeep Kumar Dhanda Mohamad Ridhuan Mohd Ali Narcisse MS Joseph Department of Medical Microbiology Faculty of Medicine and Health SciencesUniversiti Putra Malaysia43400Malaysia Department of Biomedical Science Faculty of MedicineQuest International University30250Malaysia Department of Oncology St Jude Children’s Research Hospital Memphis38105USA Institute for Medical Research Ministry of HealthMalaysia

Objective:To assess the efficacy of various types of vaccines developed for leptospirosis.Methods:A comprehensive search was conducted in three databases:PubMed,Scopus,and Cochrane Library.Two authors(YS and MN)selected the articles based on manual screening.The study eligibility criteria are all Leptospira species regardless of any cluster(pathogenic,intermediate and non-pathogenic).This study recorded articles with positive and negative results and showed a comparison among various membrane proteins as vaccine candidates.The studies on the effectiveness of outer membrane protein as vaccine candidates were also included.The articles obtained in the databases were imported into the WPS spreadsheet,and duplicate documents were removed manually.Results:A total of 24 studies were included in the review,which evaluated various types of leptospirosis vaccines.Multiple vaccines were developed and tested;however,the heterogeneity of Leptospira species pose a challenge.As an effective approach,an epitope based vaccine shows quite a promising result.However,sufficient validation,testing and clinical trials are required.Conclusions:Developing an effective vaccine for leptospirosis remains a global health priority.While significant progress has been made in recent years,there is a need for further research to optimize vaccine development and to ensure that vaccines are accessible and effective for high-risk populations.

关键词： Leptospira vaccine candidate Outer membrane protein

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SARS-CoV-2: vaccines in the pandemic era

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Military Medical Research 2021年第2期8卷 238-252页

作者： Dan-Dan Li Qi-Han Li Institute of Medical Biology Chinese Academy of Medicine Science&Peking Union Medical CollegeYunnan Key Laboratory of Vaccine Research and Development on Severe Infectious DiseasesNo.935 Jiaoling RoadKunming 650118YunnanChina

Coronavirus disease 2019(COVID-19),caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has caused millions of infections and deaths worldwide since its emergence in December 2019.As there is little or no natural immunity in the human population or specific anti-COVID-19 drugs,researchers from the government,academia and industry are developing vaccines at an unprecedented speed to halt the pandemic.In this review,the results of animal experiments and clinical trials on several vaccine technical platforms are summarized,and several challenges are also discussed to further promote the development,evaluation and application of vaccines during the challenging situation of the global pandemic.

关键词： Severe acute respiratory syndrome coronavirus 2 Coronavirus disease 2019 vaccine vaccine candidate Clinical trials

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Expression,Characterization and Immunogenicity of a Major Outer Membrane Protein from Vibrio alginolyticus

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Acta Biochimica et Biophysica Sinica 2007年第3期39卷 194-200页

作者： Ronghua QIAN~(1,2) Wuying CHU~3 Zhijuan MAO~(1,4) Chongwen ZHANG~(1,2) Yongwei WEI~2 Lian YU~2*1 Department of Biomedical Engineering,Zhejiang University,Hangzhou 310027,China 2 Institute of Preventive Veterinary Medicine,Zhejiang University,Hangzhou 310029,China 3 Institute of Subtropical Agriculture,Chinese Academy of Sciences,Changsha 410125,China 4 Ningbo Oceanography and Fishery Institute,Ningbo 315012,China DepartmentofBiomedicalEngineering ZhejiangUniversityHangzhou310027China InstituteofPreventiveVeterinaryMedicine ZhejiangUniversityHangzhou310029China InstituteofSubtropicalAgriculture ChineseAcademyofSciencesChangsha

Vibrio alginolyticus is one of the Vibrio pathogens common to humans and marine animals.During infection and induction of the host immune response,outer membrane proteins of bacteria play animportant role.In this study,an outer membrane protein gene(ompW)was cloned from V.alginolyticus andexpressed in Escherichia coli.The 645 bp open reading frame(ORF)encodes a protein of 214 amino acidresidues with a predicted molecular weight of 23.3 kDa.The amino acid sequence showed a high identitywith that of Photobacterium damselae(96.2%)and Vibrio parahaemolyticus(94.4%).The alignment analy-sis indicated that OmpW was highly conserved.Sodium dodecyl sulfate-polyacrylamide gel electrophoresisshowed that the gene was over-expressed in E.coli BL21(DE3).Western blot analysis revealed that theexpressed protein had immunoreactivity.The recombinant protein was purified by affinity chromatographyon Ni-NTA Superflow resin.Large yellow croaker vaccinated with the purified OmpW showed significantlyincreased antibody to OmpW,which could resist the infection by V.alginolyticus.A specific antibody wasdetected by enzyme-linked immunosorbent assay.This study suggested that the conserved OmpW could bean effective vaccine candidate against infection by V.alginolyticus.

关键词： Vibrio alginolyticus ompW expression characterization immunogenicity vaccine candidate

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Plasmodium vivax GPI-anchored micronemal antigen(PvGAMA) binds human erythrocytes independent of Duffy antigen status

Plasmodium vivax GPI-anchored micronemal antigen(PvGAMA) bin...

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中国动物学会寄生虫学专业委员会第十届全国寄生虫学青年工...

作者： Yang Cheng Feng Lu Bo Wang Jian Li Jin-Hee Han Daisuke Ito Deok-Hoon Kong Lubin Jiang Jian Wu Kwon-Soo Ha Eizo Takashima Jetsumon Sattabongkot Won Sun Park Seok-Ho Hong Sanjay A.Desai Louis H.Miller Takafumi Tsuboi Eun-Taek Han Department of Medical Environmental Biology and Tropical Medicine School of MedicineKangwon National University Department of Parasitology Wuxi Medical School Jiangnan University Laboratory of Malaria and Vector Research (LMVR) National Institute of Allergy and Infectious Diseases (NIAID) National Institutes of Health (NIH) Division of Malaria Research Proteo-Science Center Ehime University Department of Molecular and Cellular Biochemistry School of Medicine Kangwon National University Key Laboratory of Molecular Virology & Immunology Unit of Human Parasite Molecular and Cell Biology Institut Pasteur of Shanghai Mahidol Vivax Research Unit Faculty of Tropical Medicine Mahidol University Department of Physiology School of Medicine Kangwon National University Department of Internal Medicine School of Medicine Kangwon National University

Plasmodium vivax, a major agent of malaria in both temperate and tropical climates, has a limited capacity for infecting humans lacking the Duffy(Fy) blood group antigen as this receptor is critical for erythrocyte invasion. Recent surveys in various endemic regions, however, have reported P. vivax infections in Duffy-negative individuals, suggesting that the parasite may utilize alternative receptor-ligand pairs to complete erythrocyte invasion. Here, we identified and characterized a novel parasite ligand, GPI-anchored micronemal antigen(Pv GAMA), that can bind human erythrocytes regardless of Duffy antigen status. Specific antibodies raised against PvG AMA localize the protein to the parasite microneme, consistent with a role in invasion. These antibodies also inhibited Pv GAMA binding to erythrocytes in a dose-dependent manner. Pv GAMA appears to play a role in a sialic acid-independent, chymotrypsin-sensitive invasion pathway. Thus, Pv GAMA may be an adhesion molecule for invasion of Duffy positive and negative human erythrocytes and is an important P. vivax vaccine candidate.

关键词： Plasmodium vivax GAMA erythrocyte binding Duffy negative sialic acid-independent vaccine candidate

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Production of Plasmodium vivax Enolase in Escherichia coli and its Protective Properties

Production of Plasmodium vivax Enolase in Escherichia coli a...

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中国动物学会寄生虫学专业委员会第十届全国寄生虫学青年工...

作者： Chao Zhang Yaping Gu Jianxia Tang Feng Lu Yuanyuan Cao Huayun Zhou Guoding Zhu Jun Cao Qi Gao Key Laboratory on Technology for Disease Prevention and Control(Ministry of Health) Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology Jiangsu Institute of Parasitic Diseases Public Health Research Center Jiangnan University

Objective: Plasmodium vivax predominates in South-East Asia and the American continent, causes significant morbidity and inflicts a huge socioeconomic burden. Sequencing completion of the Plasmodium vivax genome and transcriptome provides the chance to identify antigens. Enolase is the eighth enzyme in the glycolytic pathway, which, apart from its glycolytic function, also possess antigenic properties and is present on the cell wall of many invasive organisms, such as Candida albicans. In order to assess whether enolase of Plasmodium vivax is also antigenic, in this study, we first reported the expression and purification of recombinant Plasmodium vivax enolase(r-Pven) in Escherichia coli, using prokaryotic expression vector. Methods and results: The r-Pven was expressed in soluble form in E. coli, and the expression was verified by SDS-PAGE and western blotting analysis. The r-Pven was purified to 90% purity by nickel–nitrilotriacetic acid(Ni–NTA) resin chromatography. For reactivity with r-Pven, compared with the average values of the reactivity of control serum samples, the average values of the reactivity of 99 individual serums from vivax malaria patients appeared higher, and there was significant difference between them(p=0.0117<0.05). Mice anti-r-Pven antibodies inhibited the growth of in vitro cultures of P. falciparum. Mice immunized with r-Pven showed protection against a challenge with the mouse malarial parasite Plasmodium berghei. The antibodies raised against r-Pven were specific for Plasmodium and did not react to the host tissues. Conclusion: These observations established Plasmodium vivax enolase to be a potential protective antigen.

关键词： Malaria Plasmodium vivax Enolase Prokaryotic expression vaccine candidate

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