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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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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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Construction and humoral immune response of Epstein-Barr virus latent membrane protein 2 DNA vaccine

Jianqing PAN PhD, Qin ZHANG MD, Daowen WANG MD, PhD,

《医学前沿（英文）》 2009年第3卷第4期页码 390-395 doi: 10.1007/s11684-009-0087-5

摘要： We constructed a eukaryotic expression plasmid encoding Epstein-Barr virus latent membrane protein 2 (EBV, LMP2) and evaluated its effects on humoral immunity. First, the encoding sequence of the EBV was amplified from B95−8 cell RNA by reverse transcription polymerase chain reaction (RT-PCR) and then was directionally cloned into eukaryotic expression vector pcDNA3.1. It was employed to evaluate immune response of the mice inoculated doubly with the DNA vaccine. The serum antibody against LMP2 was detected with enzyme-linked immunosorbent assay (ELISA). The recombinant plasmid pcDNA3.1- was confirmed by the restrictive endonuclease analysis and sequence analysis. The serum titer of IgG antibody against LMP2 epitope in the mice immunized with the DNA vaccine encoding LMP2 was up to 1∶4000. In conclusion, the EBV DNA vaccine can induce a strong humoral immune response in mice.

关键词： Epstein-Barr virus latent membrane protein 2 nasopharyngeal carcinoma humoral immunity

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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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工程化DNA材料构建DNA活字系统实现可持续的数据存储 Article

巩子祎, 宋理富, 裴广胜, 董雨菲, 李炳志, 元英进

《工程（英文）》 2023年第29卷第10期页码 130-136 doi: 10.1016/j.eng.2022.05.023

摘要：

DNA分子作为一种具有潜力的数据存储绿色材料，具有密度高和保存期长的优势。然而，目前DNA数据存储的数据写入依赖于DNA从头合成，写入成本高昂，且产生有害物，限制了其实际应用。在本研究中，我们开发了一种DNA活字存储系统，该系统可以利用由细胞工厂预生产的DNA活字片段进行数据写入。在这个系统中，这些预先生成的DNA片段，在这里称为“DNA活字”，是可重复使用的基本数据单元。通过这些DNA活字的快速组装来实现数据写入，从而避免了昂贵且对环境有害的DNA化学合成过程。通过DNA活字片段的反复使用和生物组装，该系统在降低写入成本方面的潜力非常突出，为经济和可持续的DNA数据存储技术开辟了一条新颖路线。

关键词：合成生物学 DNA信息存储 DNA活字存储系统经济性DNA数据存储

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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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The role of PARP1 in the DNA damage response and its application in tumor therapy

null

《医学前沿（英文）》 2012年第6卷第2期页码 156-164 doi: 10.1007/s11684-012-0197-3

摘要：

Single-strand break repair protein poly(ADP-ribose) polymerase 1 (PARP1) catalyzes the poly(ADP-ribosyl)ation of many key proteins in vivo and thus plays important roles in multiple DNA damage response pathways, rendering it a promising target in cancer therapy. The tumor-suppressor effects of PARP inhibitors have attracted significant interest for development of novel cancer therapies. However, recent evidence indicated that the underlying mechanism of PARP inhibitors in tumor therapy is more complex than previously expected. The present review will focus on recent progress on the role of PARP1 in the DNA damage response and PARP inhibitors in cancer therapy. The emerging resistance of BRCA-deficient tumors to PARP inhibitors is also briefly discussed from the perspective of DNA damage and repair. These recent research advances will inform the selection of patient populations who can benefit from the PARP inhibitor treatment and development of effective drug combination strategies.

关键词： PARP1 synthetic lethality PARP inhibitor DNA repair cancer NHEJ

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Functional role of ATM in the cellular response to DNA damage

Ming LIU, Wenxiang HU

《化学科学与工程前沿（英文）》 2011年第5卷第2期页码 179-187 doi: 10.1007/s11705-009-0268-4

摘要： Ataxia-telangiectasia mutated (ATM) plays a key role in regulating the cellular response to ionizing radiation. The tumor-suppressor gene ATM, mutations in which cause the human genetic disease ataxia telangiectasia, encodes a key protein kinase that controls the cellular response to double-stranded breaks. Activation of ATM results in phosphorylation of many downstream targets that modulate numerous damage response pathways, most notably cell cycle checkpoints. Here, we highlight some of the new developments in the field in our understanding of the mechanism of activation of ATM and its signaling pathways, explore whether DNA double-strand breaks are the sole activators of ATM and ATM-dependent signaling pathways, and address some of the prominent, unanswered questions related to ATM and its function. The scope of this article is to provide a brief overview of the recent literature on this subject and to raise questions that could be addressed in future studies.

关键词： ataxia-telangiectasia mutated (ATM) cell cycle checkpoint DNA damage signalling transduction

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Generation and repair of AID-initiated DNA lesions in B lymphocytes

null

《医学前沿（英文）》 2014年第8卷第2期页码 201-216 doi: 10.1007/s11684-014-0324-4

摘要：

Activation-induced deaminase (AID) initiates the secondary antibody diversification process in B lymphocytes. In mammalian B cells, this process includes somatic hypermutation (SHM) and class switch recombination (CSR), both of which require AID. AID induces U:G mismatch lesions in DNA that are subsequently converted into point mutations or DNA double stranded breaks during SHM/CSR. In a physiological context, AID targets immunoglobulin (Ig) loci to mediate SHM/CSR. However, recent studies reveal genome-wide access of AID to numerous non-Ig loci. Thus, AID poses a threat to the genome of B cells if AID-initiated DNA lesions cannot be properly repaired. In this review, we focus on the molecular mechanisms that regulate the specificity of AID targeting and the repair pathways responsible for processing AID-initiated DNA lesions.

关键词： class switch recombination somatic hypermutation activation-induced deaminase DNA repair genomic instability

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Molecular simulation of the interaction mechanism between CodY protein and DNA in

Linchen Yuan, Hao Wu, Yue Zhao, Xiaoyu Qin, Yanni Li

《化学科学与工程前沿（英文）》 2019年第13卷第1期页码 133-139 doi: 10.1007/s11705-018-1737-4

摘要： In , the global transcriptional regulatory factor CodY can interact with the promoter DNA to regulate the growth, metabolism, environmental adaptation and other biological activities of the strains. In order to study the mechanism of interaction between CodY and its target DNA, molecular docking and molecular dynamics simulations were used to explore the binding process at molecular level. Through the calculations of the free energy of binding, hydrogen bonding and energy decomposition, nine key residues of CodY were identified, corresponding to SER184, SER186, SER208, THR217, ARG218, SER219, ASN223, LYS242 and GLY243, among which SER186, ARG218 and LYS242 play a vital role in DNA binding. Our research results provide important theoretical guidance for using wet-lab methods to study and optimize the metabolic network regulated by CodY.

关键词： CodY DNA molecular docking molecular dynamics

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Environmental pollution and DNA methylation: carcinogenesis, clinical significance, and practical applications

null

《医学前沿（英文）》 2015年第9卷第3期页码 261-274 doi: 10.1007/s11684-015-0406-y

摘要：

Environmental pollution is one of the main causes of human cancer. Exposures to environmental carcinogens result in genetic and epigenetic alterations which induce cell transformation. Epigenetic changes caused by environmental pollution play important roles in the development and progression of environmental pollution-related cancers. Studies on DNA methylation are among the earliest and most conducted epigenetic research linked to cancer. In this review, the roles of DNA methylation in carcinogenesis and their significance in clinical medicine were summarized, and the effects of environmental pollutants, particularly air pollutants, on DNA methylation were introduced. Furthermore, prospective applications of DNA methylation to environmental pollution detection and cancer prevention were discussed.

关键词： environmental pollution DNA methylation cancer biomarker diagnosis therapy prevention

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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