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/i> and RR2 gene deletion affects the immunogenicity of a live attenuated pseudorabies virus vaccinecandidate in natural pig host

Shijun YAN,He YAN,Chaolin ZHANG,Tongyan WANG,Qingyuan YANG,Zhe SUN,Yan XIAO,Feifei TAN,Xiangdong LI,Kegong TIAN

《农业科学与工程前沿（英文）》 2016年 第3卷 第1期   页码 81-86 doi: 10.15302/J-FASE-2016088

摘要： As virulence-determining genes, and 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 and genes based on a / / 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 as its parent strain. In an animal study, the virus could elicit humoral immune responses shown by generation of gB-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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immune mapped protein 1 (NcIMP1) is a novel vaccine candidate against neosporosis

Xia CUI,Daoyu YANG,Tao LEI,Hui WANG,Pan HAO,Qun LIU

《农业科学与工程前沿（英文）》 2015年 第2卷 第1期   页码 66-72 doi: 10.15302/J-FASE-2015047

摘要： The immune mapped protein 1 (NcIMP1) was identified as a membrane protein, and a previous study indicated that NcIMP1 could be a promising vaccine candidate against neosporosis. In this study, the immune response and protection efficacy of NcIMP1 were evaluated. The coding sequence of NcIMP1 was inserted into the eukaryotic expression vector pcDNA 3.1(+), resulting in the recombination plasmid pcDNA-IMP1, 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 2 × 10 was performed 14 days after the last immunization. The results showed that the mice immunized with pcDNA-IMP1 developed a high level of specific antibody responses against recombinant NcIMP1, with a mixed IgG1/IgG2a response and a predominance of IgG2a 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 pcDNA-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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Innovation-driven trend shaping COVID-19 vaccine development in China

《医学前沿（英文）》 doi: 10.1007/s11684-023-1034-6

摘要： Confronted with the coronavirus disease 2019 (COVID-19) pandemic, China has become an asset in tackling the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and mutation, with several innovative platforms, which provides various technical means in this persisting combat. Derived from collaborated researches, vaccines based on the spike protein of SARS-CoV-2 or inactivated whole virus are a cornerstone of the public health response to COVID-19. Herein, we outline representative vaccines in multiple routes, while the merits and plights of the existing vaccine strategies are also summarized. Likewise, new technologies may provide more potent or broader immunity and will contribute to fight against hypermutated SARS-CoV-2 variants. All in all, with the ultimate aim of delivering robust and durable protection that is resilient to emerging infectious disease, alongside the traditional routes, the discovery of innovative approach to developing effective vaccines based on virus properties remains our top priority.

关键词： SARS-CoV-2     COVID-19 vaccine     vaccine development    

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Optimising the oil phases of aluminium hydrogel-stabilised emulsions for stable, safe and efficient vaccine

《化学科学与工程前沿（英文）》 2022年 第16卷 第6期   页码 973-984 doi: 10.1007/s11705-021-2123-1

摘要： To increase antibody secretion and dose sparing, squalene-in-water aluminium hydrogel (alum)-stabilised emulsions (ASEs) have been developed, which offer increased surface areas and cellular interactions for higher antigen loading and enhanced immune responses. Nevertheless, the squalene (oil) in previous attempts suffered from limited oxidation resistance, thus, safety and stability were compromised. From a clinical translational perspective, it is imperative to screen the optimal oils for enhanced emulsion adjuvants. Here, because of the varying oleic to linoleic acid ratio, soybean oil, peanut oil, and olive oil were utilised as oil phases in the preparation of aluminium hydrogel-stabilised squalene-in-water emulsions, which were then screened for their stability and immunogenicity. Additionally, the underlying mechanisms of oil phases and emulsion stability were unravelled, which showed that a higher oleic to linoleic acid ratio increased anti-oxidative capabilities but reduced the long-term storage stability owing to the relatively low zeta potential of the prepared droplets. As a result, compared with squalene-in-water ASEs, soybean-in-water ASEs exhibited comparable immune responses and enhanced stability. By optimising the oil phase of the emulsion adjuvants, this work may offer an alternative strategy for safe, stable, and effective emulsion adjuvants.

关键词： pickering emulsion     vaccine adjuvant     alum-stabilised emulsion     oleic to linoleic acid ratio     stability    

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Antitumor immunity of human SART3 gene vaccine against mouse tumor

HE Yu, YANG Shuhua, LIU Yong, LI Tao

《医学前沿（英文）》 2008年 第2卷 第1期   页码 51-57 doi: 10.1007/s11684-008-0010-5

摘要： To determine whether squamous cell carcinoma antigen recognized by human T cell 3 (SART3) gene can induce antitumor immunity against tumor cells which express the gene, we constructed mouse tumor cells expressing human SART3 (LM8-SART3) and carried out experiments . After subcutaneous injection with SART3 gene vaccine, cytotoxic T lymphocyte (CTL) activity was measured using Cell Counting Kit-8. As for the part, C3H mice were divided into several groups. One group was challenged with tumor cells after immunity. Another group was treated with the vaccine after tumor implantation. It was found that human SART3 DNA vaccine can elicit a specific CTL reaction from the mouse splenocytes. After vaccination, tumor occurrence and tumor growth speed was reduced. The vaccine also shows activity in tumor treatment. We conclude that the human SART3 DNA vaccine can induce antitumor ability against tumor cells expressing human SART3 (LM8-SART3) which may provide new possibilities in antitumor therapy.

关键词： antitumor therapy     occurrence     implantation     DNA vaccine     SART3 DNA    

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核酸疫苗研发态势与发展建议

李爱花,杨雪梅,孙轶楠,苑亚坤,杨俊涛

《中国工程科学》 2021年 第23卷 第4期   页码 153-161 doi: 10.15302/J-SSCAE-2021.04.018

摘要：

应对新型冠状病毒肺炎（COVID-19）疫情防控的迫切需求，核酸疫苗以其快速高效的优点得到了疫苗研发领域的高度重视，特别是信使核糖核酸（mRNA）疫苗的研发进程显著加快，首次获批上市并在人体中使用。本文从核酸疫苗及相关技术概念、研发轨迹与发展趋势等方面总结梳理核酸疫苗的研发态势，辨识核酸疫苗特征，分析 COVID-19 疫情对 mRNA疫苗研究的促进作用，梳理核酸疫苗拓展应用的主要领域，针对可能存在的技术性、安全性问题开展深入讨论。研究建议，从改良目的基因表达、完善递送系统、提高免疫应答、增强 mRNA 稳定性及易存性等方面着手，着力开展核酸疫苗的关键技术开发；严格监管核酸疫苗的安全性和有效性；引导利益相关方对具有安全性风险、可能对肿瘤与传染病防控带来颠覆性影响的 mRNA 疫苗技术开展改进研究，注重技术研发的前瞻布局并促进应用转化。

关键词： 核酸疫苗     脱氧核糖核酸（DNA）疫苗     核糖核酸（RNA）疫苗     信使核糖核酸（mRNA）疫苗     新型冠状病毒肺 炎     肿瘤    

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Broadly neutralizing antibodies and vaccine design against HIV-1 infection

Qian Wang, Linqi Zhang

《医学前沿（英文）》 2020年 第14卷 第1期   页码 30-42 doi: 10.1007/s11684-019-0721-9

摘要： Remarkable progress has been achieved for prophylactic and therapeutic interventions against human immunodeficiency virus type I (HIV-1) through antiretroviral therapy. However, vaccine development has remained challenging. Recent discoveries in broadly neutralizing monoclonal antibodies (bNAbs) has led to the development of multiple novel vaccine approaches for inducing bNAbs-like antibody response. Structural and dynamic studies revealed several vulnerable sites and states of the HIV-1 envelop glycoprotein (Env) during infection. Our review aims to highlight these discoveries and rejuvenate our endeavor in HIV-1 vaccine design and development.

关键词： HIV-1     broadly neutralizing antibodies     Env conformational states     vaccine design     SOSIP    

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Protection of inactivated vaccine against SARS-CoV-2 infections in patients with comorbidities: a prospective

《医学前沿（英文）》   页码 867-877 doi: 10.1007/s11684-023-0995-9

摘要： Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of inactivated vaccines is not well characterized in people with comorbidities, who are at high risk of severe infection. We compared the risk of SARS-CoV-2 infection after complete vaccination with Sinopharm/BBIBP in people with comorbidities (e.g., autoimmune diseases, cardiovascular disease, chronic lung disease, and diabetes) with healthy individuals using a Cox-proportional hazard model. In July–September 2021, a total of 10 548 people (comorbidities, 2143; healthy, 8405) receiving the complete primary series of vaccination with Sinopharm/BBIBP in Bangkok, Thailand were prospectively followed for SARS-CoV-2 infection through text messaging and telephone interviewing for 6 months. A total of 295 infections from 284 participants were found. HRs (95% CI) of individuals with any comorbidities did not increase (unadjusted, 1.02 (0.77–1.36), P = 0.89; adjusted, 1.04 (0.78–1.38), P = 0.81). HRs significantly increased in the subgroup of autoimmune diseases (unadjusted, 2.64 (1.09–6.38), P = 0.032; adjusted, 4.45 (1.83–10.83), P = 0.001) but not in cardiovascular disease, chronic lung disease, or diabetes. The protection against SARS-CoV-2 infection of the Sinopharm vaccine was similar in participants with any comorbidities vs. healthy individuals. However, the protection appeared lower in the subgroup of autoimmune diseases, which may reflect suboptimal immune responses among these people.

关键词： COVID-19     Sinopharm/BBIBP vaccine     immunocompromised patients     real-world    

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Corrosion mechanisms of candidate structural materials for supercritical water-cooled reactor

Lefu ZHANG, Fawen ZHU, Rui TANG

《能源前沿（英文）》 2009年 第3卷 第2期   页码 233-240 doi: 10.1007/s11708-009-0024-y

摘要： Nickel-based alloys, austenitic stainless steel, ferritic/martensitic heat-resistant steels, and oxide dispersion strengthened steel are presently considered to be the candidate structural or fuel-cladding materials for supercritical water-cooled reactor (SCWR), one of the promising generation IV reactor for large-scale electric power production. However, corrosion and stress corrosion cracking of these candidate alloys still remain to be a major problem in the selection of nuclear fuel cladding and other structural materials, such as water rod. Survey of literature and experimental results reveal that the general corrosion mechanism of those candidate materials exhibits quite complicated mechanism in high-temperature and high-pressure supercritical water. Formation of a stable protective oxide film is the key to the best corrosion-resistant alloys. This paper focuses on the mechanism of corrosion oxide film breakdown for SCWR candidate materials.

关键词： supercritical water-cooled reactor     general corrosion     oxide film     corrosion mechanism    

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Human monoclonal antibodies as candidate therapeutics against emerging viruses

null

《医学前沿（英文）》 2017年 第11卷 第4期   页码 462-470 doi: 10.1007/s11684-017-0596-6

摘要：

The emergence of new pathogens, such as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and Ebola virus, poses serious challenges to global public health and highlights the urgent need for novel antiviral approaches. Monoclonal antibodies (mAbs) have been successfully used to treat various diseases, particularly cancer and immunological disorders. Antigen-specific mAbs have been isolated using several different approaches, including hybridoma, transgenic mice, phage display, yeast display, and single B-cell isolation. Consequently, an increasing number of mAbs, which exhibit high potency against emerging viruses in vitro and in animal models of infection, have been developed. In this paper, we summarize historical trends and recent developments in mAb discovery, compare the advantages and disadvantages of various approaches to mAb production, and discuss the potential use of such strategies for the development of antivirals against emerging diseases. We also review the application of recently developed human mAbs against SARS-CoV, MERS-CoV, and Ebola virus and discuss prospects for the development of mAbs as therapeutic agents against emerging viral diseases.

关键词： human monoclonal antibodies     emerging infectious diseases     SARS-CoV     MERS-CoV     Ebola virus    

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Immunogenicity and protective immunity against otitis media caused by pneumococcus in mice of Hib conjugate vaccine

null

《医学前沿（英文）》 2016年 第10卷 第4期   页码 490-498 doi: 10.1007/s11684-016-0470-y

摘要：

This study evaluated the immunogenicity and protective immunity of a Hemophilus influenzae b (Hib) polysaccharide conjugate vaccine with the pneumococcal surface adhesin A (PsaA) protein carrier in young mice. The Hib polysaccharide was conjugated with the rPsaA protein carrier, which was produced using recombinant DNA technology. A total of 15 young mice aged 3 weeks to 5 weeks were immunized with the conjugate vaccine, and another 15 young mice of the same age were immunized with the licensed Hib-tetanus toxoid (TT) vaccine. Furthermore, the third group of 15 young mice was inoculated with phosphate buffer saline as control. The immunized mice were inoculated with pneumococcus in the middle ear. Results showed that IgG antibody responses against both the PsaA protein and Hib polysaccharide were observed in the Hib-PsaA group. However, no statistical difference was observed in the titer of IgG against the Hib polysaccharide between Hib-PsaA and Hib-TT groups. The elimination rate of pneumococcus and the inflammation of the middle ear showed the effectiveness of protective immunity against otitis media caused by pneumococcus. Our results suggest that the Hib polysaccharide can be successfully conjugated with rPsaA via amide condensation. This new Hib-PsaA conjugate vaccine can induce both anti-PsaA and anti-Hib immune responses in young mice and elicit effective protection against acute otitis media caused by pneumococcus.

关键词： conjugate vaccine     pneumococcal surface adhesin A     Hemophilus influenzae b     immunogenicity     otitis media    

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药品监管科学推动中国新冠病毒疫苗研发概述 Review

黄志明, 付志浩, 王军志

《工程（英文）》 2022年 第10卷 第3期   页码 127-132 doi: 10.1016/j.eng.2022.01.001

摘要：

监管科学是一门综合应用自然科学、社会科学和人文科学，开发新工具、新标准和新方法，以评估受监管产品的安全性、有效性、质量和性能的学科。监管科学研究的根本目的是为行政决策提供技术支撑。在甲型H1N1流感、严重急性呼吸综合征（SARS）和中东呼吸综合征（MERS）等传染病大流行期间，监管科学研究有力支持了抗病毒药物和疫苗的研发。特别在新型冠状病毒（简称新冠病毒）肺炎（COVID-19）疫情大流行期间，药品监管科学支持下的疫苗研发在疫情防控中发挥了重要作用。本文总结了中国疫苗产业、新冠病毒疫苗研发以及疫苗监管科学发展的总体概况。此外，本文重点从国家规划、法律法规、技术指南、质量控制和疫苗上市后监管等方面，回顾和分析了监管科学研究为推动中国新冠病毒疫苗研发所发挥的重要作用。本文为当前大流行阶段以及后疫情时代的疫苗研发策略制定提供参考，并为将来如何更好地应对新发和再发传染病提供借鉴和指导。

关键词： 监管科学     新冠病毒疫苗     疫苗产业    

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virological characteristics of human immunodeficiency virus type 1 superinfection: implications in vaccine

null

《医学前沿（英文）》 2017年 第11卷 第4期   页码 480-489 doi: 10.1007/s11684-017-0594-8

摘要：

Superinfection is frequently detected among individuals infected by human immunodeficiency virus type I (HIV-1). Superinfection occurs at similar frequencies at acute and chronic infection stages but less frequently than primary infection. This observation indicates that the immune responses elicited by natural HIV-1 infection may play a role in curb of superinfection; however, these responses are not sufficiently strong to completely prevent superinfection. Thus, a successful HIV-1 vaccine likely needs to induce more potent and broader immune responses than those elicited by primary infection. On the other hand, potent and broad neutralization responses are more often detected after superinfection than during monoinfection. This suggests that broadly neutralizing antibodies are more likely induced by sequential immunization of multiple different immunogens than with only one form of envelope glycoprotein immunogens. Understanding why the protection from superinfection by immunity induced by primary infection is insufficient and if superinfection can lead to cross-reactive immune responses will be highly informative for HIV-1 vaccine design.

关键词： human immunodeficiency virus type I     superinfection     incidence     immune response    

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Mutation profiling of 16 candidate genes in

Yang Zhang, Fang Wang, Xue Chen, Wenjing Liu, Jiancheng Fang, Mingyu Wang, Wen Teng, Panxiang Cao, Hongxing Liu

《医学前沿（英文）》 2019年 第13卷 第2期   页码 229-237 doi: 10.1007/s11684-018-0616-1

摘要： This retrospective analysis aimed to investigate the mutation profile of 16 common mutated genes in acute myeloid leukemia (AML) patients. A total of 259 patients who were diagnosed of AML were enrolled in this study. Mutation profiling of 16 candidate genes were performed in bone marrow samples by using Sanger sequencing. We identified at least 1 mutation in 199 of the 259 samples (76.8%), and 2 or more mutations in 31.7% of samples. was the most common mutated gene (16.2%, 42/259), followed by (15.1%, 39/259), (14.7%, 38/259), and (13.5%, 35/259). Concurrence was observed in 97.1% of the mutated cases and in 29.6% of the double mutated cases. Distinct patterns of co-occurrence were observed for different hotspot mutations within the gene: mutations were associated with and/or mutations, whereas mutations co-occurred with mutations only. Concurrence was also observed in 86.6% of epigenetic regulation genes, most of which co-occurred with mutations. The results showed certain rules in the mutation profiling and concurrence of AML patients, which was related to the function classification of genes. Defining the mutation spectrum and mutation pattern of AML will contribute to the comprehensive assessment of patients and identification of new therapeutic targets.

关键词： leukemia     myeloid     acute     gene     mutation    

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Vaccine therapies for chronic hepatitis B: can we go further?

null

《医学前沿（英文）》 2014年 第8卷 第1期   页码 17-23 doi: 10.1007/s11684-014-0313-7

摘要：

Chronic hepatitis B is a major health burden worldwide. In addition to the recent progress in antiviral treatment, therapeutic vaccination is a promising new strategy for the control of chronic hepatitis B. On the basis of the major specific and non-specific immune dysregulations and defects in chronic hepatitis B patients, this paper presents the peptide and protein-based, DNA-based, cell-based, and antigen-antibody-based therapeutic vaccines, which have undergone clinical trials. The advantages, disadvantages, and future perspectives for these therapeutic vaccines are discussed.

关键词： chronic hepatitis B     therapeutic     antigen-antibody complexes     DNA     vaccine    

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标题 作者 时间 类型 操作

/i> and RR2 gene deletion affects the immunogenicity of a live attenuated pseudorabies virus vaccinecandidate in natural pig host

Shijun YAN,He YAN,Chaolin ZHANG,Tongyan WANG,Qingyuan YANG,Zhe SUN,Yan XIAO,Feifei TAN,Xiangdong LI,Kegong TIAN

期刊论文

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

Xia CUI,Daoyu YANG,Tao LEI,Hui WANG,Pan HAO,Qun LIU

期刊论文

Innovation-driven trend shaping COVID-19 vaccine development in China

期刊论文

Optimising the oil phases of aluminium hydrogel-stabilised emulsions for stable, safe and efficient vaccine

期刊论文

Antitumor immunity of human SART3 gene vaccine against mouse tumor

HE Yu, YANG Shuhua, LIU Yong, LI Tao

期刊论文

核酸疫苗研发态势与发展建议

李爱花,杨雪梅,孙轶楠,苑亚坤,杨俊涛

期刊论文

Broadly neutralizing antibodies and vaccine design against HIV-1 infection

Qian Wang, Linqi Zhang

期刊论文

Protection of inactivated vaccine against SARS-CoV-2 infections in patients with comorbidities: a prospective

期刊论文

Corrosion mechanisms of candidate structural materials for supercritical water-cooled reactor

Lefu ZHANG, Fawen ZHU, Rui TANG

期刊论文

Human monoclonal antibodies as candidate therapeutics against emerging viruses

null

期刊论文

Immunogenicity and protective immunity against otitis media caused by pneumococcus in mice of Hib conjugate vaccine

null

期刊论文

药品监管科学推动中国新冠病毒疫苗研发概述

黄志明, 付志浩, 王军志

期刊论文

virological characteristics of human immunodeficiency virus type 1 superinfection: implications in vaccine

null

期刊论文

Mutation profiling of 16 candidate genes in

Yang Zhang, Fang Wang, Xue Chen, Wenjing Liu, Jiancheng Fang, Mingyu Wang, Wen Teng, Panxiang Cao, Hongxing Liu

期刊论文

Vaccine therapies for chronic hepatitis B: can we go further?

null

期刊论文