治疗性疫苗研究进展

治疗性疫苗通过打破机体的免疫耐受,提高机体的特异性免疫反应,对一些目前尚无有效治疗药物的传染性疾病、肿瘤等起到治疗作用。介绍了治疗性疫苗的概况、机理和临床最新进展。     

预防性及治疗性乙型肝炎疫苗的研究进展

乙型病毒性肝炎(viral hepatitis type B,简称乙肝)是一个严重的世界性公共卫生问题,该疾病在健康人群中发病率极高,同时也在慢性乙肝患者中引起极高的死亡率。乙肝是一种可预防的疾病,用于预防的乙肝疫苗经过三代发展,已有安全、有效的疫苗上市,该疫苗的使用使慢性乙肝患者(包括肝细胞性肝癌患者)的发病率急剧下降。但目前尚无清除乙肝患者体内病毒的特效药物,增强机体免疫反应的治疗性疫苗可能是抗病毒药物的替代品。针对乙肝患者的治疗性疫苗正被广泛研究,包含重组蛋白疫苗、DNA疫苗和脂肽疫苗等。现就国内外预防性及治疗性乙肝疫苗的研究进展作一概述。     

治疗性结核病疫苗研究进展

治疗性结核病疫苗主要用于接种已感染结核分枝杆菌的个体,包括化学药物治疗的患者和潜伏感染者。治疗性疫苗可逆转发生在疾病进展期的非保护性免疫反应,使其向Th1型反应发展;能打破机体的免疫耐受,有效激发宿主针对结核分枝杆菌的以抗原为基础的细胞免疫反应,诱发抗原特异性的细胞毒性T淋巴细胞免疫反应,来清除胞内寄生的结核分枝杆菌。治疗性疫苗将有助于防止潜伏结核病的复发;与药物联合使用以提高药物的治疗效果,尤其是针对耐药结核病的治疗。     

治疗性疫苗在慢性感染性疾病中的应用

在慢性感染性疾病中,患者往往存在免疫功能异常,表现为药物治疗反应差,于是治疗性疫苗又重新引起了人们的兴趣。治疗性疫苗通过使用新型佐剂,载体,树突细胞过继免疫,同种异体免疫治疗等方法,改善抗原呈递细胞（APC）功能,改善患者免疫耐受情况,从而刺激机体恢复特异性免疫应答,达到根除病原,防止复发的目的。     

乙肝DNA疫苗的研究进展

核酸疫苗包括DNA疫苗和RNA疫苗,目前研究以DNA疫苗为主。乙肝DNA疫苗不仅能诱导机体细胞介导的体液免疫反应,而且还能诱导机体细胞介导的特异性细胞免疫反应,CTL活性增强,在乙型肝炎预防和治疗中具有广阔的应用前景。本文就近几年有关乙肝DNA疫苗的进展作了综述。     

肿瘤疫苗的研究进展

作为一种前景光明的肿瘤治疗方式,肿瘤疫苗能帮助机体产生针对肿瘤抗原的特异性免疫应答和长期的免疫记忆来治疗肿瘤,是癌症免疫治疗领域重要的研究方向。目前,肿瘤疫苗按制剂方式主要可以分为四类,即细胞疫苗、病毒疫苗、多肽类疫苗和核酸类疫苗。这些疫苗能通过增强机体内抗肿瘤免疫反应而发挥清除肿瘤细胞、抑制肿瘤生长的功能。该综述将对肿瘤疫苗的作用机制、基础研究与临床试验的最新进展进行讨论,以期为深入理解肿瘤疫苗、开发新型肿瘤疫苗提供有益的参考。     

动态

新型结核病疫苗研制成功　德国马普学会传染病生物学研究所研制出一种新型结核病疫苗 ,能够有效增强机体免疫力并能有的放矢地消灭结核病菌。疫苗具有一种特殊的蛋白质分子 ,能够刺激产生T淋巴细胞 ,增强机体免疫系统功能 ,对吞噬细胞内的病菌进行有效攻击。疫苗的有效免疫期为 1 5 0天 ,预计将在一年后进入临床试验。日本开发出早老性痴呆治疗性疫苗　据《日本经济新闻》报道 ,早老性痴呆症 (阿尔茨海默氏症 )是贝塔淀粉样蛋白在脑细胞中沉淀 ,大脑发生萎缩引起的痴呆症。日本国立疗养所中部医院长寿医疗研究中心的原英夫等研究员利用基因…     

Clin Cancer Res:科学家有望开发出抵御早期乳腺癌的新型疫苗

正免疫系统的反常调节和抑制作用往往会诱发癌症的产生,很多治疗性策略旨在重新激活机体的免疫系统来识别癌细胞并且靶向杀灭癌细胞;近日一项刊登在国际杂志Clinical Cancer Research上的研究报告中,来自莫非特癌症研究中心的研究人员通过研究开发出了一种能够靶向作用乳腺癌细胞表面HER2蛋白的树突细胞疫苗,这种新型疫苗能够安全有效地刺激机体免疫反应,有效逆转早期乳腺癌的发生。     

DNA疫苗机制研究进展

DNA疫苗可全面激活机体的免疫反应,具有安全,热稳定性,价廉等优点,尤其是激活的CTL活性将使之在慢性感染性疾病以及肿瘤治疗领域具有广阔应用前景,但DNA疫苗诱发机体产生免疫反应的机制尚有许多问题有待于搞清,现就DNA疫苗机制及研究进展进行综述。     

黏膜免疫:结核疫苗免疫的新途径

结核分枝杆菌主要是通过呼吸道传播,而机体的呼吸道黏膜免疫又是抵御从黏膜途径入侵的外来物质的第一道防线。因此,诱导有效的黏膜免疫应答对结核分枝杆菌感染的预防和治疗性疫苗的研制具有重要的价值。     

A comparison and critical analysis of preclinical anticancer vaccination strategies

Anticancer vaccines have been extensively studied in animal models and in clinical trials. While vaccination can lead to tumor protection in numerous murine models, objective tumor regressions after anticancer vaccination in clinical trials have been rare. B16 is a poorly immunogenic murine melanoma that has been extensively used in anticancer vaccination experiments. Because B16 has been widely used, different vaccination strategies can be compared. We reviewed the results obtained when B16 was treated with five common vaccine types: recombinant viral vaccines, DNA vaccines, dendritic cell vaccines, whole-tumor vaccines, and peptide vaccines. We also reviewed the results obtained when B16 was treated with vaccines combined with adoptive transfer of tumor antigen-specific T cells. We found several characteristics of vaccination regimens that were associated with antitumor efficacy. Many vaccines that incorporated xenogeneic antigens exhibited more potent anticancer activity than vaccines that were identical except that they incorporated the syngeneic version of the same antigen. Interleukin-2 enhanced the antitumor efficacy of several vaccines. Finally, several effective regimens generated large numbers of tumor antigen-specific CD8(+) T cells. Identification of vaccine characteristics that are associated with antitumor efficacy may aid in the development of more effective anticancer vaccination strategies.     

A combination of intradermal jet-injection and electroporation overcomes in vivodose restriction of DNA vaccines

Development of various vaccines for prostate cancer (PCa) is becoming an active research area. PCa vaccines are perceived to have less toxicity compared with the available cytotoxic agents. While various immune-based strategies can elicit anti-tumour responses, DNA vaccines present increased efficacy, inducing both humoural and cellular immunity. This immune activation has been proven effective in animal models and initial clinical trials are encouraging. However, to validate the role of DNA vaccination in currently available PCa management paradigms, strong clinical evidence is still lacking. This article provides an overview of the basic principles of DNA vaccines and aims to provide a summary of preclinical and clinical trials outlining the benefits of this immunotherapy in the management of PCa.     

肿瘤基因疫苗的研究进展

基因疫苗技术自从20世纪90年代问世以来被迅速应用到传染病、免疫缺陷、肿瘤等重大疾病的预防和治疗的研究中,有一部分已经进入临床试验阶段.肿瘤基因疫苗可以打破免疫耐受,增强免疫原性,诱导机体产生针对肿瘤的体液和细胞反应,既有预防又有治疗肿瘤的作用.能够防治肿瘤的基因疫苗发展迅猛,主要包括与肿瘤相关抗原（TAAs）有关的全长、表位、独特型（Id）和融合DNA疫苗,能够自主复制的RNA疫苗,与树突细胞（DCs）相关的肿瘤基因疫苗等.肿瘤基因疫苗的分子作用机制及其存在的弊端也日益成为关注的问题.     

mRNA疫苗在疾病预防与治疗中的研究进展与展望

基于信使RNA(messenger RNA, mRNA)的核酸疫苗是近年来兴起的一种mRNA技术。mRNA疫苗比传统疫苗有许多优点,能够实现快速、经济、高效的生产。单个mRNA疫苗可以编码多种抗原,增强对特定病原体的免疫反应,提高疾病的治疗效率,以单一配方针对多种病原微生物或疾病。mRNA疫苗相关技术在新型冠状病毒肺炎疫情防控中被视作一种革命性的疫苗技术,以创纪录的速度完成研发并成功应用。由于mRNA自身稳定性差,新型递送系统的开发与应用至关重要。随着mRNA相关药理学的深入研究,mRNA疫苗的临床应用进入了一个崭新的阶段。近年来。mRNA疫苗在传染性疾病预防、肿瘤治疗等方面获得充分发展并取得了一定的研究成果,对其进行概述并进行一定程度的展望。     

Highly potent mRNA based cancer vaccines represent an attractive platform for combination therapies supporting an improved therapeutic effect

Direct vaccination with mRNA encoding tumor antigens is a novel and promising approach in cancer immunotherapy. CureVac's mRNA vaccines contain free and protamine-complexed mRNA. Such two-component mRNA vaccines support both antigen expression and immune stimulation. These self-adjuvanting RNA vaccines, administered intradermally without any additional adjuvant, induce a comprehensive balanced immune response, comprising antigen specific CD4+ T cells, CD8+ T cells and B cells. The balanced immune response results in a strong anti-tumor effect and complete protection against antigen positive tumor cells. This tumor inhibition elicited by mRNA vaccines is a result of the concerted action of different players. After just two intradermal vaccinations, we observe multiple changes at the tumor site, including the up-regulation of many genes connected to T and natural killer cell activation, as well as genes responsible for improved infiltration of immune cells into the tumor via chemotaxis. The two-component mRNA vaccines induce a very fast and boostable immune response. Therefore, the vaccination schedules can be adjusted to suit the clinical situation. Moreover, by combining the mRNA vaccines with therapies in clinical use (chemotherapy or anti-CTLA-4 antibody therapy), an even more effective anti-tumor response can be elicited. The first clinical data obtained from two separate Phase I/IIa trials conducted in PCA (prostate cancer) and NSCLC (non-small cell lung carcinoma) patients have shown that the two-component mRNA vaccines are safe, well tolerated and highly immunogenic in humans.     

Combined modality immunotherapy and chemotherapy: a new perspective

The results of recent clinical trials have demonstrated that cancer vaccines continue to struggle to achieve tangible clinical benefits as monotherapy. Tumor-induced abnormalities in the immune system hamper anti-tumor T cell responses limiting the effectiveness of cancer immunotherapy. Recently, evidence has been mounting to suggest that immunotherapy has the possibility of achieving better success when used in combination with conventional chemotherapy. In clinical trials, immune responses elicited by cancer vaccines appear to augment the effectiveness of subsequent conventional cancer therapies.     

登革病毒3'UTRΔ30系列疫苗的研究进展

登革病毒引发的登革热等疾病每年在全球范围内造成了相当大的经济、医疗、社会负担,严重威胁到人类生命健康。在目前研究的各种登革病毒疫苗中,采用反向遗传技术制得的3'UTRΔ30系列减毒活疫苗由于其免疫原性好,效价高,成本低等特点,在临床试验中展现出良好保护作用,研究推进快。能对四种血清型登革病毒都产生均衡免疫保护的3'UTRΔ30四联疫苗已处于III期临床试验阶段,效力强,不良反应少,待随访期结束后有望上市,是当今最有前景的登革减毒灭活疫苗之一。为更深入了解3'UTRΔ30系列疫苗,现主要从起源、制备方法、临床研究等方面进行介绍。     

Tuberculosis vaccine development: recent progress

Recent years have seen a renewed effort to develop new vaccines against tuberculosis. As a result, several promising avenues of research have developed, including the production of recombinant vaccines, auxotrophic vaccines, DNA vaccines and subunit vaccines. In this article we briefly review this work, as well as consider the pros and cons of the animal models needed to test these new vaccines. Screening to date has been carried out in mouse and guinea pig models, which have been used to obtain basic information such as the effect of the vaccine on bacterial load, and whether the vaccine can prevent or reduce lung pathology. The results to date lead us to be optimistic that new candidate vaccines could soon be considered for evaluation in clinical trials.     

Challenges to licensure of enterovirus 71 vaccines

Human enteroviruses usually cause self-limited infections except polioviruses and enterovirus 71 (EV71), which frequently involve neurological complications. EV71 vaccines are being evaluated in humans. However, several challenges to licensure of EV71 vaccines need to be addressed. Firstly, EV71 and coxsackievirus A (CA) are frequently found to co-circulate and cause hand-foot-mouth disease (HFMD). A polyvalent vaccine that can provide protection against EV71 and prevalent CA are desirable. Secondly, infants are the target population of HFMD vaccines and it would need multi-national efficacy trials to prove clinical protection and speed up the licensure and usage of HFMD vaccines in children. An international network for enterovirus surveillance and clinical trials is urgently needed. Thirdly, EV71 is found to evolve quickly in the past 15 years. Prospective cohort studies are warranted to clarify clinical and epidemiological significances of the antigenic and genetic variations between different EV71 genogroups, which is critical for vaccine design.     

Development of mucosal influenza inactivated vaccines

In this review recent data on the development of mucosal influenza inactivated vaccines with the use of mucosoadhesive adjuvants are presented. After the intranasal administration of such vaccines the formation of not only systemic, but also local immunity (IgA antibodies), as well as cross protection against the variants of influenza virus within its serotype, can be observed. Some mucosal influenza vaccines have passed clinical tests. Certain drawbacks of Escherichia thermolabile enterotoxin, used as mucosoadhesive adjuvant, and difficulties which may arise in mass immunization with mucosal vaccines due to the necessity of introducing them in two or three intranasal administrations are indicated.