免疫佐剂在肿瘤免疫疗法中的应用进展

免疫疗法是预防和治疗疾病的有效手段之一。近年来,肿瘤免疫疗法已成为一种新型治疗方法,相关肿瘤疫苗已在多种肿瘤的治疗中被证明有效。然而,在肿瘤疫苗的设计中,肿瘤抗原免疫原性弱、应答率低等问题是目前面对的一大挑战,佐剂的加入为问题的解决提供了一种新的方法和思路。免疫佐剂在提高肿瘤抗原免疫原性、激活机体适应性免疫应答等方面起着十分重要的作用。为了解近几年免疫佐剂的发展及其研究现状,针对目前常用的抗肿瘤佐剂进行综述,并总结了其对免疫系统的作用机制,为后续的疫苗设计策略提供帮助。     

黏膜免疫佐剂的研究进展

佐剂对于增强疫苗的免疫效果以及改变免疫应答类型发挥着非常重要的作用。然而,在人用疫苗中可使用的佐剂数量有限,尤其是有效的黏膜免疫佐剂缺乏。黏膜免疫佐剂能有效提高抗原的免疫原性,减少抗原用量或免疫接种次数,促进抗原提呈细胞的提呈作用,从而增强特异性免疫应答;但黏膜免疫佐剂安全性、有效性、免疫效力仍未达到理想的效果,需进一步深入研究。就目前常用的几种黏膜免疫佐剂的研究进展作一综述。     

纳米疫苗在肿瘤免疫疗法中的应用

近年来肿瘤免疫疗法成为癌症治疗领域的热点,其中结合肿瘤疫苗和纳米技术的纳米疫苗为肿瘤免疫疗法提供了新思路.纳米疫苗可以实现疫苗和佐剂的共载,且智能化的纳米载体进一步实现了抗原有效的靶向递送,促进了抗原的摄取和递呈,激活抗原特异性免疫应答,有效杀伤肿瘤细胞.本文就纳米疫苗的原理、优势、纳米材料的类型、临床疗效进行综述,为后期纳米疫苗的设计提供更可靠的参考依据.     

新型疫苗佐剂的研究进展

与传统的灭活或活体疫苗相比,由基因工程重组抗原或化学合成多肽组成的现代疫苗往往存在免疫原性弱等问题,需要新型的免疫佐剂来增强其作用。尽管传统的铝盐佐剂是目前唯一全球公认的人用佐剂,但存在激发细胞免疫应答能力差等不足,因此,需要研发更为安全有效的人用新型佐剂,尤其是安全无毒、能够刺激较强细胞免疫应答的佐剂,以及适合粘膜疫苗、DNA疫苗和癌症疫苗的免疫佐剂。分析阐述了新型佐剂研究状况和佐剂发展方向,并进一步对新型佐剂的临床前和临床试验研究以及已批准上市的新型疫苗佐剂进行了综述。     

固有免疫学的研究进展及其对研制新型免疫佐剂的启示

近年来,亚单位疫苗、DNA重组疫苗、合成肽疫苗等新型疫苗不断涌现,这些疫苗纯度高、特异性强。但其分子小,免疫原性较差,难以诱导机体产生有效的免疫应答,需添加佐剂来增强其免疫原性或增强宿主对抗原的保护性应答。免疫学的研究阐明了固有免疫如何调节适应性免疫。随着固有免疫学的发展和生化技术的提高,开发特异性更强、生物安全性更高的免疫佐剂越来越受到重视。对佐剂的分类、作用机理,固有免疫学的研究进展进行了综述,并就未来发展趋势提出自己的观点,为临床应用和进一步研制高效、低毒的免疫佐剂提供了参考。     

核酸疫苗佐剂的研究进展

免疫佐剂是一种免疫调节剂,可增强抗原的免疫原性、提高免疫效果。为增强疫苗的免疫原性,在病毒性疫苗、DNA疫苗、多肽疫苗的研制中通常需加入免疫佐剂。随着DNA疫苗研究的深入和扩展,推动了用于提高DNA疫苗免疫效果的免疫佐剂的研究。本文就常用佐剂的研究进展作一综述。     

关于黏膜免疫佐剂的研究现状

佐剂（Aldjuvants）是先于抗原或与抗原同时应用,能非特异性地改变或增强机体对抗原的特异性免疫应答,能增强相应抗原的免疫原性或改变免疫反应类型,而本身并无抗原性的物质,又称免疫佐剂或抗原佐剂。1925年法国免疫学家拉蒙发现在疫苗中加入某些与之无关的物质可以特异性地增强机体的免疫反应。此后,许多国家都不同程度地开展了这方面的研究。     

双特异抗体定向运载抗原作为一种新型佐剂系统的研究进展

目前采用基因重组等生物技术制备了大量的纯化亚单位疫苗或合成疫苗,这些疫苗的免疫原性很弱,需要佐剂的帮助才能有效地引发抗体应答。传统的佐剂具有很多本身无法克服的缺陷,促使人们研究开发新的佐剂系统。本文对双特异抗体的概念、Ｔ细胞在免疫应答中的作用及抗原的定向运送、双特异抗体介导的抗原定向运送及佐剂效应等方面对双特异抗体定向运送抗原作为一个新的佐剂系统给予了较为详细的阐述     

新型疫苗佐剂的研究进展

近年来,核酸疫苗、基因工程疫苗、合成肽疫苗等新型疫苗的研究取得快速的发展,但这些疫苗与传统的灭活或活体疫苗相比,往往存在免疫原性差等问题,因此需要佐剂来增强其作用。佐剂已被证明是疫苗中的关键成分,佐剂种类众多,尚无统一的分类方法,目前应用最多的佐剂是铝佐剂和弗氏佐剂,但随着新型疫苗的开发,新型佐剂的开发必不可少。根据目前佐剂的研究现状,主要从免疫调节分子类佐剂、抗原递送类佐剂、复合佐剂3个方面进行分析阐述,以期对佐剂的研制提供参考。     

免疫佐剂作用机制及CpG ODN作为新型佐剂的研究

免疫佐剂通过免疫调节作用等5种方式发挥功能,借助佐剂的非抗原特异性的多克隆激活是天然免疫细胞可能的作用机制.大部分佐剂通过直接参与天然免疫事件而间接/直接影响获得性免疫应答,不同的佐剂可针对不同的事件发挥作用.CpG ODN作为佐剂的优势在新近的研究中被逐渐发现.     

A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

正Dear Editor,In December 2019, a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19) in Wuhan, Hubei, China(Wu et al. 2020; Zhu et al. 2020). So far, this virus has spread to all areas of China and even to other countries. The epidemic has caused 67,102 confirmed infections with 1526 fatal cases     

Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site

Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.     

Comparative morphology of the carpel in the Liliaceae: Hewardieae, Petrosavieae, and Tricyrteae

The young pistils in the melanthioid tribes, Hewardieae, Petrosavieae and Tricyrteae, are uniformly tricarpellate and syncarpous. They lack raphide idioblasts. All are multiovulate, with bitegmic ovules. The Petrosavieae are marked by the presence of septal glands and incomplete syncarpy. Tepals and stamens adhere to the ovary in the Hewardieae and the Petrosavieae but not in the Tricyrteae. Two vascular bundles occur in the stamens of the Hewartlieae and Tricyrtis latifolia. Ventral bundles in the upper part of the ovary of the Hewardieae are continuous with compound septal bundles and placental bundles in the lower part. Putative ventral bundles occur in the alternate position in the Tricyrteae and putative placental bundles in the opposite. position in the Petrosavieae. The dichtomously branched stigma in each carpel of the Tricyrteae is supplied by a bifurcated dorsal bundle.     

Enterovirus 71 3C proteolytically processes the histone H3 N-terminal tail during infection

Highlights
1. The N-terminal tail of histone H3 is specifically cleaved during EV71 infection.
2. Viral protease 3C is identified as a protease responsible for proteolytically processing the N-terminal H3 tail.
3. Our finding reveals a new epigenetic regulatory mechanism for Enterovirus 71 in virus-host interactions.     

Detection of EBV and HHV6 in the Brain Tissue of Patients with Rasmussen’s Encephalitis

Rasmussen’s encephalitis (RE) is a rare pediatric neurological disorder, and the exact etiology is not clear. Viral infection may be involved in the pathogenesis of RE, but conflicting results have reported. In this study, we evaluated the expression of both Epstein-Barr virus (EBV) and human herpes virus (HHV) 6 antigens in brain sections from 30 patients with RE and 16 control individuals by immunohistochemistry. In the RE group, EBV and HHV6 antigens were detected in 56.7% (17/30) and 50% (15/30) of individuals, respectively. In contrast, no detectable EBV and HHV6 antigen expression was found in brain tissues of the control group. The co-expression of EBV and HHV6 was detected in 20.0% (6/30) of individuals. In particular, a 4-year-old boy had a typical clinical course, including a medical history of viral encephalitis, intractable epilepsy, and hemispheric atrophy. The co-expression of EBV and HHV6 was detected in neurons and astrocytes in the brain tissue, accompanied by a high frequency of CD8⁺ T cells. Our results suggest that EBV and HHV6 infection and the activation of CD8⁺ T cells are involved in the pathogenesis of RE.     

Perinatal Vertical Transmission of Chikungunya Virus in Ruili,a Town on the Border between China and Myanmar

正Dear Editor,Chikungunya virus (CHIKV), an arbovirus in the family of Togaviridae, genus Alphavirus, is transmitted by the A.aegyptii or A. albopictus mosquito, and causes disease in humans characterized by fever, rash, and arthralgia (Silva and Dermody 2017; Suhrbier 2019). It was first reported in 1953 in Tanzania, and caused only a few outbreaks and sporadic cases in Africa and Asia in last century. However, in the epidemic in 2004, CHIKV acquired mutations that conferred enhanced transmission by the A. albopictus mosquito(Schuffenecker et al. 2006). Since then, it has successively caused outbreaks in Africa, the Indian Ocean, South East Asia, the South America, and Europe (Zeller et al. 2016).     

Development of a Novel Reverse Transcription Loop-Mediated Isothermal Amplification Method for Rapid Detection of SARS-CoV-2

In conclusion, the novel visual RT-LAMP assay is a simple, rapid, and sensitive approach for detection of SARS-CoV-2, and it is ready for application in primary care and community hospitals or health care centers, and even patients' own houses in response to the current SARS-CoV-2 epidemic because the assay does not require sophisticated equipment and skilled personnel. Furthermore, it is also ready to be used in fields for screening samples from wild animals and environments to facilitate the identification of potential intermediate hosts that mediate the cross-species transmission of SARS-CoV-2 from bats to humans.