Status on the diagnosis and treatment of BK virus infection

BK病毒（BKV）属于人类多瘤病毒中的一个亚型。BKV在普通人群中隐性感染率高达80%。近年来,随着器官移植术的广泛开展以及强效免疫抑制剂的大量使用,在免疫抑制和免疫低下的人群中,由潜伏于体内的BKV重新被激活而引起的BKV相关肾病（BKVAN）、出血性膀胱炎、输尿管狭窄等疾病越来越受到医学界的关注。目前对BKV感染缺乏明确有效的预防措施及抗病毒药物,因此早期监测器官移植术后患者体内的BKV载量、减少免疫抑制剂的使用量、及时调整免疫抑制剂治疗方案并辅助使用其他抗病毒药物对预防BKV相关疾病的发生尤为重要。文章就BKV感染相关的疾病及其临床症状、生物学特征、感染机制以及当前国内外诊断及治疗研究现状进行综述。BK virus （BKV） belongs to a subtype of human polyomavirus. Recessive infection rate of BKV in general population is about 80%. With expanded use of organ transplantation in recent years where strong immunosuppression is essential,BKV associated nephropathy（BKVAN）,hemorrhagic cystitis,ureterostenosis and other associated diseases due to the reactivation of latent BKV in immunosuppressed or immunocompromised populations are becoming more of a concern in medical community. Since the prevention measures and effective antiviral drugs for BKV are rather limited,the effective means for reducing BK associated morbidity and mortality due to BKV associated diseases are the early monitoring of viral loads,reducing the usage of immunosuppressant,adjusting immunosuppressant treatment regime and using adjuvant therapies. This review describes the clinical symptoms,biology,mechanisms and the advances in the diagnosis and treatment of BKV at home and abroad

Current status of vaccine development against leishmaniasis

利什曼病是由利什曼原虫引起的一种人兽共患寄生虫病,分布于全球90多个国家,每年新发利什曼病患者130多万,有2万~3万例死亡,给全球尤其是发展中; 国家带来沉重的社会经济及医疗负担。目前针对利什曼病的防治措施主要为控制传染源和药物治疗,但均无法消除利什曼病。疫苗接种是行之有效的并具社会经济效; 益的控制利什曼病的防治手段。因此,利什曼病疫苗的研发具有十分重要的现实意义。本文重点就利什曼原虫致病机制及各类利什曼病疫苗的研究现状进行综述。Leishmaniasis is a zoonotic disease caused by Leishmania parasites.; Currently, leishmaniasis has affected 12 million people in over 90; countries, with 1.3 million reported cases each year and 20 -30 thousand; deaths. The disease causes a large social and economic burden; particularly in developing countries. Current strategies for; leishmaniasis control include controlling the source of infection and; drug treatment, both of which, however, cannot eliminate the disease.; Effective vaccination would be an ideal approach to control; leishmaniasis. Here, we review the pathogenic mechanism of Leishmania,; the existing vaccines for veterinary use, and human vaccine development; efforts against the disease

Enhanced vaccine accessibility through innovative regulatory sciences

疫苗储存运输要遵循冷链运输(cold; chain,CC)的要求,这很大程度上限制了疫苗的接种和普及,尤其是在那些贫困偏远地区。为扩大疫苗可及性,世界卫生组织(World Health; Organization,WHO)于2012年首次提出了受控温度链(controlled temperature; chain,CTC)法规,即在政府部门和WHO的监管下,在有充分热稳定性数据支持的前提下,若申报CTC的疫苗在不低于40 ℃下存放至少3; d后仍能保证效力,则该疫苗在免疫供应链后期无需冷链运输。CTC法规已成功应用在包括MenAfriVac~在内的4个商品化疫苗上。本文介绍了CTC; 法规的内容和应用情况,通过科学监管提高疫苗可及性,减少不必要的浪费。The need to keep vaccine in a traditional cold chain (CC) is a; constraining factor for many immunization campaigns,particularly in the; resource-limited countries. Increased flexibility with an approach newly; introduced in 2012 was implemented with meningitis a; vaccine,MenAfriVac~,across sub-Saharan Africa,after thorough review of; the scientific data by regulatory authorities and World Health; Organization (WHO). This approach was termedcontrolled temperature; chain(CTC) by allowing the vaccines to be exposed at temperatures of up; to 40 ℃ for a minimum of three days prior to the administration of the; vaccine. There are four vaccines were licensed for CTC,including; MenAfriVac~. This article introduces the details and the applications of; CTC. More efforts are underway to fully realize the potentials of the; CTC strategy for increased vaccine accessibility and reduced wastage

双膦酸盐类药物用于肿瘤辅助治疗的临床研究进展

双膦酸盐是用于骨骼疾病及钙代谢性疾病治疗的一类药物,主要用于治疗骨质疏松症、佩吉特病、高钙血症等。同时临床研究显示双膦酸盐还可用于多发性骨髓瘤、乳腺癌、肾癌、前列腺癌等疾病的辅助治疗,改善患者的临床结局,尤其是唑来膦酸盐的抗肿瘤效果更具优势,被广泛应用于多种恶性肿瘤的临床研究。本文就双膦酸盐在肿瘤辅助治疗中的临床研究进展进行综述。国家自然科学基金面上项目(31670939

数学模型在HPV疫苗经济学评估中的研究进展

人乳头状瘤病毒(HuMAn PAPIllOMA VIruS,HPV)持续感染引起宫颈癌、肛门癌和生殖器疣等多种HPV相关疾病。其中,宫颈癌和生殖器疣已严重威胁到人群的生命健康[1-6],其防治工作成为当前亟待解决的公共卫生问题。预防性HPV疫苗已经被证明可以有效阻断HPV感染和降低人群宫颈癌和生殖器疣发病率,并且其已在多个国家获得了使用许可[4]。HPV疫苗接种方案的经济学评估对科学规划HPV疫苗接种方案和优化卫生资源配置有着重要作福建省科技厅科技计划项目(2013R0091); 教育部人文社会科学研究项目(12YJA790030); 福建省自然科学基金计划资助项目(2012J01303

人乳头瘤病毒疫苗的临床效用及其经济学研究

人乳头瘤病毒(HPV)的持续感染可引起多种威胁人类健康的疾病,造成巨大的经济负担。研究表明,接种HPV疫苗可有效阻断HPV感染,从而降低相关疾病的发病率和死亡率。目前已有3种HPV预防性疫苗(Gardasil?,Merck;Cervarix?,GSK;Gardasil9,Merck)上市,临床效用突出并取得了可观的健康经济效益。为加速HPV疫苗在国内推广,进一步减轻个人和社会的经济负担,本文通过检索Pubmed、SpringerLink和中国知网等数据库,总结了多个国家HPV相关疾病经济负担的情况,以及接种HPV疫苗后取得的临床效用及经济效益,并对影响HPV疫苗经济效益的因素进行了分析。国家自然科学基金(81471934

Monoclonal antibodies against HPV11 virus-like particles: functional characteristics and application on quality assessment

目的分析和鉴定抗HPV11病毒样颗粒(virus-like particle,VLP)鼠源单克隆抗体的性质,筛选性质和生物学活性较优的抗体,并初步应用于抗原或疫苗的质量分析。方法分别利用间接ELISA法和Western blot对HPV11的22株单克隆抗体的亚类、与HPV11 VLP的结合能力和构象敏感性进行检测;采用血凝抑制实验对单克隆抗体的血凝抑制活性进行分析;运用基于假病毒的抗体中和实验对单克隆抗体的中和活性进行鉴定,选出中和活性高的单抗进行两两配对,采用双抗夹心ELISA法捕获单抗并筛选合适的配对双抗。结果对22株单抗的性质进行了详细和完整的鉴定,并根据构象敏感性进行排序,筛选出6株型别特异、结合活性强且中和活性高的单抗(2A2、4A1-3、16G7、14A6、9C12和19C7);成功建立了基于单抗的双抗夹心(14A6∶Ag∶9C12-HRP)ELISA定量分析方法。结论获得了较全面的HPV11 VLP单抗性质信息,建立了重组HPV11抗原质量分析的双抗夹心ELISA法,为HPV11抗原的生命周期管理或尖锐湿疣疫苗的研发、工艺优化、产品放行和稳定性研究等提供了技术支持。Objective To quantitatively analyze the characteristics of a panel of murine anti-human papillomavirus( HPV) 11 L1-derived virus-like particle( VLP) monoclonal antibodies( m Abs) and establish the m Ab-based methods for antigen quality analysis. Methods A panel of 22 murine anti-HPV11 m Abs were characterized in details with their isotype,and binding affinity,conformational sensitivity were examined quantitatively in the direct binding ELISA and Western blot. The hemagglutination inhibition activity of m Abs were identified using the hemagglutination inhibition assay and the pseudovirus( Ps V) neutralization efficiency were examined quantitatively using the Ps V-based neutralization assay. The type-specific, highly conformational sensitive and neutralizing m Abs were selected to be used in the sandwich ELISA assay. Results Based on the quantitative and semi-quantitative results,six type-specific,highly conformational sensitive and neutralizing m Abs( 2A2,4A1-3,16G7,14A6,9C1 and 19C7) were identified. These m Abs,along with 10D6 were screened as the capture m Ab or as the detection m Ab in the sandwich ELISA. Conclusion The binding affinity,conformational sensitivity and neutralization efficiency of anti-HPV11 m Abs were characterized in details. A m Ab-based sandwich ELISA assay( 14A6∶Ag∶9C12-HRP) were developed,which could be used in the in vitro potency analysis of HPV11 VLP-based vaccine.重大新药创制(2015ZX09101034

Development of interleukin-21 as a therapeutic drug

白细胞介素21; (IL-21)是一种具有多效免疫调节活性的细胞因子,参与先天性免疫反应和适应性免疫反应的多个环节,与自身免疫性疾病、肿瘤、病毒感染等疾病的发病过; 程相关。研究表明,在动物模型中通过增强或抑制IL-21的生物学功能对多种疾病具有治疗意义,多项以重组人IL-21为受试药物的临床试验已经开展。本; 文就IL-21的生物学功能,以及IL-21作为生化药物在临床治疗中的研究进展和应用前景进行阐述。Interleukin-21 (IL-21) is a cytokine with broad pleiotropic actions that; plays an important role in both innate and adaptive immune responses.; IL-21 participates in pathogenesis processes of many diseases, such as; autoimmune disease, tumor, virus infections and so on. Enhancing or; inhibiting the activity of IL-21 has shown to have certain therapeutic; effects in animal models of a wide range of diseases. Various clinical; trials using recombinant human IL-21 as drug candidates are on-going; towards the development of IL-21 as a therapeutic drug. This article; reviewed the biological function and research progress and application; prospect of IL-21 as a biochemical drug in clinical treatment

B族链球菌疫苗研究现状及展望

B族链球菌(group B streptococcus,GBS)主要危害新生儿、孕妇以及免疫力低下人群,能够引发早产、死产,还能引起脓毒症、菌血症和脑膜炎等多种疾病。使用抗生素是预防GBS的主要手段,但随着抗生素耐药性的逐渐增强,急需发展一种安全、有效的GBS疫苗,用于预防GBS感染。目前已有部分GBS候选疫苗进入临床试验阶段,同时也有部分疫苗处于临床前研究阶段。本文就这些具有临床使用潜力的GBS疫苗的研究现状进行综述。国家基金(81471934);;分子疫苗学和分子诊断学国家重点实验室自主研究课题资助项目(课题编号:2016ZY005

Disassembly and reassembly improves morphology and thermal stability of human papillomavirus type 16 virus-like particles

Recombinant human papillomavirus (HPV) 16 L1 protein self-assembles into virus-like particles (VLPs) with diameters of 40 to 60 nm, which are key components in prophylactic HPV vaccines. Marked improvement in morphology and thermal stability on VLP disassembly and reassembly was demonstrated at production scale. Differential scanning calorimetry showed enhanced conformational stability as indicated by the unfolding temperatures and peak heights/areas. Cloud point studies indicated (1) a much lower propensity for post-reassembly VLPs to aggregate during a time course study and (2) much higher cloud point temperatures. In-solution atomic force microscopy showed more uniform size distribution and fully closed particles, with evidence of virion-like assembly revealed by the structural details from a single particle image. Similar approaches for the reassembly of other recombinant VLPs with intrinsic conformational switches would be expected to improve the particle properties and render nanoparticles more suitable for use as vaccines or therapeutics. From the Clinical Editor: The authors of this study demonstrated that recombinant human papillomavirus 16 L1 protein self-assembles into virus-like particles (VLPs) with marked improvement in morphology and thermal stability on VLP disassembly and reassembly at production scale. This is expected to render these nanoparticles more suitable for use as vaccines or therapeutics. (C) 2012 Elsevier Inc. All rights reserved