DNA疫苗及其在流感病毒疫苗研究中的应用

DNA疫苗能够诱导广谱免疫反应，已被广泛应用于预防性疫苗和针对各种感染性疾病、肿瘤、自身免疫性疾病和过敏性疾病的免疫治疗的临床试验。自DNA疫苗技术出现，A型流感病毒就与其紧密地联系在一起，已被广泛应用于小鼠和其他动物模型以研究DNA疫苗的免疫作用和机理。     

治疗性疫苗的研究进展

由微生物传染的慢性病大多是较难治疗的疾病，尤其文谱耐药的细菌性和某些病毒性疾患。例如：慢性结核病、乙型肝炎、艾滋病等都是很难治愈的疾病，目前尚无有产对策。疫苗作为免疫制品主要用于预防传染性疾病，而对其治疗用途的探索较少。虽然如此，国内外合肥市有一些研究报告，如泌司法部系统慢性细菌感染、疱疹性角膜溃疡、乙型肝炎等。采用疫苗治疗，并取得一定的疗效。卡介苗用于膀胱癌辅助治疗的效果，可认为是非特异作用所致，但大多治疗用疫苗的作用机理未能进一步研究。本刊与卫生部医学分子病毒学重点实验室上海联合召开的学术报告会上，闻玉梅教授总结分析了国内外文献和自己的研究结果，提出治疗性疫苗的开发是综合微生物学与免疫学理论及应用研究的一个新领域。此文具有学术新颖性和创造性，值得微生物学和免疫学界的研究工作者特别是从事生物制品研究的人员一读和参考。     

TCR DNA疫苗及其在自身免疫性疾病中应用的研究进展

TCR DNA疫苗是一种治疗性基因疫苗,在自身免疫性疾病、肿瘤和移植排斥反应的治疗中可以选择性抑制或杀伤致病性T细胞克隆,具有很好的应用前景.本文对近年来文献中关于TCR、TCR DNA疫苗的特点及其在自身免疫病治疗中的应用及相关研究进展进行了综述.     

治疗性疫苗的研究进展

随着人们在免疫学及生物化学领域的研究中不断取得重大的突破,一种全新概念的疫苗--治疗性疫苗的研究迅速发展起来.治疗性疫苗通过改善和增强靶抗原的摄人、表达、处理、递呈,从根本上重新唤起机体对靶抗原的免疫应答能力,从而打破机体的免疫耐受、增强机体特异性免疫反应,能够对一些目前尚无有效治疗方法的慢性传染性疾病及肿瘤等起到治疗作用.目前治疗性疫苗在某些病毒性传染病、细菌性传染病、自身免疫病及肿瘤等方面都进行了大量研究,并取得了一定成就.     

治疗性HBV DNA疫苗的研究进展

乙型肝炎病毒（HBV）的持续感染可引起肝脏疾患，甚至肝硬化和原发性肝细胞癌。近年来，HBV DNA疫苗在治疗慢性HBV携带者和慢性乙型肝炎方面越来越引起人们的重视。本文主要就治疗性HBV DNA疫苗的构成、治疗慢性乙型肝炎的依据及其研究进展进行综述。     

调节性B细胞的研究进展

B细胞主要通过递呈抗原和分泌各种抗体发挥免疫学作用.近来研究发现,在B细胞中存在一种新的细胞亚群——调节性B细胞,它们可以通过分泌白细胞介素-10和转化生长因子-β1等抑制性细胞因子抑制获得性免疫介导的炎症反应发展和(或)加快炎症的恢复.相关研究表明这种细胞在感染性疾病、自身免疫性疾病、肿瘤中发挥重要作用.本文综述了调节性B细胞的发现与来源、免疫调节作用机制及其与相关疾病的研究进展.     

结核病治疗性疫苗的研究进展

耐药结核分枝杆菌的出现以及由于免疫功能失衡导致的免疫耐受是阻碍结核病有效治疗的两个重要原因。治疗性疫苗能通过对已感染结核分枝杆菌的机体产生二次免疫激发,打破机体的免疫耐受,诱导保护性免疫应答而达到清除结核分枝杆菌的目的。目前,结核病治疗性疫苗研究主要集中在DNA疫苗、亚单位疫苗、减毒活疫苗和死疫苗上。因其可纠正机体失衡的免疫状态,且对耐药性的结核分枝杆菌可产生同样的清除作用,所以,近年来结核病治疗性疫苗逐渐受到人们的关注和重视并取得了较大发展。     

TCR DNA疫苗及其在自身免疫性疾病中应用的研究进展

TCR DNA疫苗是一种治疗性基因疫苗,在自身免疫性疾病、肿瘤和移植排斥反应的治疗中可以选择性抑制或杀伤致病性T细胞克隆,具有很好的应用前景。本文对近年来文献中关于TCR、TCR DNA疫苗的特点及其在自身免疫病治疗中的应用及相关研究进展进行了综述。     

结核病治疗性疫苗的研究进展

耐药结核分枝杆菌的出现以及由于免疫功能失衡导致的免疫耐受是阻碍结核病有效治疗的两个重要原因.治疗性疫苗能通过对已感染结核分枝杆菌的机体产生二次免疫激发,打破机体的免疫耐受,诱导保护性免疫应答而达到清除结核分枝杆菌的目的.目前,结核病治疗性疫苗研究主要集中在DNA疫苗、亚单位疫苗、减毒活疫苗和死疫苗上.因其可纠正机体失衡的免疫状态,且对耐药性的结核分枝杆菌可产生同样的清除作用,所以,近年来结核病治疗性疫苗逐渐受到人们的关注和重视并取得了较大发展.     

结核病治疗性疫苗的研究进展

耐药结核分枝杆菌的出现以及由于免疫功能失衡导致的免疫耐受是阻碍结核病有效治疗的两个重要原因.治疗性疫苗能通过对已感染结核分枝杆菌的机体产生二次免疫激发,打破机体的免疫耐受,诱导保护性免疫应答而达到清除结核分枝杆菌的目的.目前,结核病治疗性疫苗研究主要集中在DNA疫苗、亚单位疫苗、减毒活疫苗和死疫苗上.因其可纠正机体失衡的免疫状态,且对耐药性的结核分枝杆菌可产生同样的清除作用,所以,近年来结核病治疗性疫苗逐渐受到人们的关注和重视并取得了较大发展.     

Hepatitis B vaccines: Protective efficacy and therapeutic potential

Worldwide, two billion people have at some time been infected by hepatitis B virus, 370 millions suffer from chronic infection and around one million die each year from HBV-related liver diseases of which liver cancer is the ultimate stage. Vaccination is the measure that is most effective in reducing the global incidence of hepatitis B and hepatitis B vaccines have now been available for over 20 years. The first hepatitis B vaccine was prepared from inactivated hepatitis B surface antigen particles purified from plasma of asymptomatic carriers of hepatitis B virus. Knowledge of the structure and genomic organization of hepatitis B virus has led to development of the first DNA recombinant vaccine. In preventing hepatocellular carcinoma development, hepatitis B virus vaccines are considered as the first available cancer vaccine. HBV vaccines have recently taken on a new role as therapeutic vaccines as an attempt to cure or to control hepatitis B virus infection in persistently infected individuals.     

Development of tuberculosis vaccines in clinical trials: Current status

Tuberculosis (TB ) is an important infectious disease worldwide. Currently, Bacillus Calmette‐Guérin (BCG ) remains the only TB vaccine licensed for human use. This TB vaccine is effective in protecting children against severe military TB but offers variable protective efficacy in adults. Therefore, new vaccines against TB are needed to overcome this serious disease. At present, around 14 TB vaccine candidates are in different phases of clinical trials. These TB vaccines in clinical evaluation can be classified into two groups including preventive pre‐ and post‐exposure vaccines: subunit vaccines (attenuated viral vectors or adjuvanted fusion proteins), and whole‐cell vaccines (genetically attenuated Mycobacterium tuberculosis (M. tb ), recombinant BCG , killed M. tb or M. vaccae ). Although, over the last two decades a great progress in the search for a more effective TB vaccine has been demonstrated there is still no replacement for the licensed BCG vaccine. This article summarizes the current status of TB vaccine development and identifies crucial gaps of research for the development of an effective TB vaccine in all age groups.     

Immunology of gut mucosal vaccines

Understanding the mechanisms underlying the induction of immunity in the gastrointestinal mucosa following oral immunization and the cross-talk between mucosal and systemic immunity should expedite the development of vaccines to diminish the global burden caused by enteric pathogens. Identifying an immunological correlate of protection in the course of field trials of efficacy, animal models (when available), or human challenge studies is also invaluable. In industrialized country populations, live attenuated vaccines (e.g. polio, typhoid, and rotavirus) mimic natural infection and generate robust protective immune responses. In contrast, a major challenge is to understand and overcome the barriers responsible for the diminished immunogenicity and efficacy of the same enteric vaccines in underprivileged populations in developing countries. Success in developing vaccines against some enteric pathogens has heretofore been elusive (e.g. Shigella). Different types of oral vaccines can selectively or inclusively elicit mucosal secretory immunoglobulin A and serum immunoglobulin G antibodies and a variety of cell-mediated immune responses. Areas of research that require acceleration include interaction between the gut innate immune system and the stimulation of adaptive immunity, development of safe yet effective mucosal adjuvants, better understanding of homing to the mucosa of immunologically relevant cells, and elicitation of mucosal immunologic memory. This review dissects the immune responses elicited in humans by enteric vaccines.     

YF17D-based vaccines – standing on the shoulders of a giant

Live-attenuated yellow fever vaccine (YF17D) was developed in the 1930s as the first ever empirically derived human vaccine. Ninety years later, it is still a benchmark for vaccines made today. YF17D triggers a particularly broad and polyfunctional response engaging multiple arms of innate, humoral and cellular immunity. This unique immunogenicity translates into an extraordinary vaccine efficacy and outstanding longevity of protection, possibly by single-dose immunization. More recently, progress in molecular virology and synthetic biology allowed engineering of YF17D as a powerful vector and promising platform for the development of novel recombinant live vaccines, including two licensed vaccines against Japanese encephalitis and dengue, even in paediatric use. Likewise, numerous chimeric and transgenic preclinical candidates have been described. These include prophylactic vaccines against emerging viral infections (e.g. Lassa, Zika and SARS-CoV-2) and parasitic diseases (e.g. malaria), as well as therapeutic applications targeting persistent infections (e.g. HIV and chronic hepatitis), and cancer. Efforts to overcome historical safety concerns and manufacturing challenges are ongoing and pave the way for wider use of YF17D-based vaccines. In this review, we summarize recent insights regarding YF17D as vaccine platform, and how YF17D-based vaccines may complement as well as differentiate from other emerging modalities in response to unmet medical needs and for pandemic preparedness.     

Nucleic acid vaccines

There are no adequate vaccines against some of the new or reemerged infectious scourges such as HIV and TB. They may require strong and enduring cell-mediated immunity to be elicited. This is quite a task, as the only known basis of protection by current commercial vaccines is antibody. As DNA or RNA vaccines may induce both cell-mediated and humoral immunity, great interest has been shown in them. However, doubt remains whether their efficacy will suffice for their clinical realization. We look at the various tactics to increase the potency of nucleic acid vaccines and divided them broadly under those affecting delivery and those affecting immune induction. For delivery, we have considered ways of improving uptake and the use of bacterial, replicon or viral vectors. For immune induction, we considered aspects of immunostimulatory CpG motifs, coinjection of cytokines or costimulators and alterations of the antigen, its cellular localization and its anatomical localization including the use of ligand-targeting to lymphoid tissue. We also thought that mucosal application of DNA deserved a separate section. In this review, we have taken the liberty to discuss these enhancement methods, whenever possible, in the context of the underlying mechanisms that might argue for or against these strategies.     

肿瘤免疫治疗研究进展

肿瘤细胞可通过一系列免疫逃避机制躲避机体免疫攻击,从而在体内肆意繁殖,侵犯机体正常组织.近年来,随着肿瘤学、免疫学以及分子生物学等相关学科的迅速发展和交叉渗透,免疫学治疗方法因其能有效杀伤肿瘤细胞且对机体副作用较小,越来越受到人们的重视,其疗效评价也因免疫治疗的特殊性而有别于一般的实体瘤治疗.就肿瘤免疫治疗的最新进展作一综述.     

治疗性人乳头瘤病毒疫苗研究进展

人乳头瘤病毒是以表皮细胞为感染对象的小型DNA病毒,HPV感染与子宫颈癌的发生、发展有着十分密切的关系.宫颈癌位居女性恶性肿瘤的第二位,且呈逐年上升的趋势.已上市的疫苗主要用于预防HPV的感染,对已感染HPV人群的治疗效果欠佳,治疗性疫苗可以通过诱导特异性的细胞免疫应答,阻止甚至清除HPV感染引起的病变及肿瘤.动物实验和临床试验结果显示,治疗性HPV疫苗在治疗HPV感染相关疾病有重要作用.因此,治疗性HPV疫苗的研制及应用已成为近年来研究热点.