新型狂犬病减毒活疫苗研究的重大突破

最近狂犬病疫苗研究取得重大突破.新型狂犬病减毒活疫苗效力更高而且高度安全,甚至有可能用于狂犬病发病后的早期治疗.这是狂犬病疫苗诞生一百多年来的一个重要里程碑.此文对狂犬病疫苗研究取得的重大突破、决定狂犬病病毒致病性和免疫原性的相关因素及新型狂犬病减毒活疫苗的主要优点作一综述.     

新型狂犬病减毒活疫苗研究的重大突破

最近狂犬病疫苗研究取得重大突破.新型狂犬病减毒活疫苗效力更高而且高度安全,甚至有可能用于狂犬病发病后的早期治疗.这是狂犬病疫苗诞生一百多年来的一个重要里程碑.此文对狂犬病疫苗研究取得的重大突破、决定狂犬病病毒致病性和免疫原性的相关因素及新型狂犬病减毒活疫苗的主要优点作一综述.     

灭活病毒疫苗研制现状

当前,世界上广泛使用的疫苗有灭活疫苗和减毒活疫苗两种,这两种疫苗对一些病毒性疾病的预防均取得了重大的成就.虽然二十年来发展减毒活疫苗是一种世界性的趋向.但在许多国家中仍然使用灭活疫苗,并致力于改进灭活疫苗的质量,不少资料证实,脊髓灰质炎、乙型脑炎和狂犬病灭活疫苗不仅能控制疾病的发生,且能产生持久免疫力,     

DNA疫苗研究进展

裸露DNA技术为亚单位疫苗的发展提供了一条崭新的途径.DNA疫苗兼有重组亚单位疫苗的安全性和减毒活疫苗诱导全面免疫应答的高效力,已成为疫苗研究领域中的热点之一.抗流感、艾滋病、狂犬病、乙型肝炎、结核病、疟疾和利什曼病等疾病的DNA疫苗的动物实验已取得可喜结果,该疫苗的最大优点是有可能对变异迅速的病原微生物提供交叉防御作用.本文对DNA疫苗的研究状况作一简述.     

乙型脑炎病毒及疫苗研究进展

乙型脑炎病毒是黄病毒科中致病性最强的病毒之一,目前对该病毒的分子生物学研究进展较快.现阶段国内外主要使用三种类型疫苗,即鼠脑纯化灭活疫苗、原代地鼠肾细胞灭活疫苗和原代地鼠肾细胞减毒活疫苗.灭活疫苗和减毒活疫苗各有利弊.基因工程疫苗(包括载体重组活疫苗、嵌合减毒活疫苗、病毒样颗粒、亚单位疫苗及DNA疫苗)成为乙型脑炎疫苗发展的方向.     

结核病疫苗研究进展

目前结核病疫情非常严峻,而唯一可用的疫苗卡介苗效果并不理想.因此,需要研发更安全有效和实用价廉的新型疫苗.此文综述了目前正在研发的新型结核病疫苗的研究进展,这些疫苗包括重组卡介苗、减毒活疫苗、亚单位疫苗、DNA疫苗和病毒载体疫苗.     

呼吸道合胞病毒减毒活疫苗研制进展

人呼吸道合胞病毒(resipiratory syncytial virus,RSV)是世界范围内儿童下呼吸道感染的主要病原体,但其疫苗的开发面临许多困难和挑战.随着反向遗传学及相关技术和工具的应用,RSV疫苗,尤其是减毒活疫苗的研制已经取得很大进展.此文就RSV减毒活疫苗研发的主要突破和研究进展进行综述.     

病毒性疫苗渗透压摩尔浓度的质量控制

目的  通过检测6种病毒性疫苗成品的渗透压摩尔浓度,比较不同疫苗检测均值的差异,并观察同种疫苗检测值的批间稳定性,为增加病毒性疫苗质量控制手段提供依据。方法  采用冰点下降法检测麻疹减毒活疫苗、风疹减毒活疫苗、麻疹腮腺炎联合减毒活疫苗、麻疹腮腺炎风疹联合减毒活疫苗、水痘减毒活疫苗、流感病毒裂解疫苗的渗透压摩尔浓度,对检测值进行统计学处理,计算变异系数。以麻疹腮腺炎风疹联合减毒活疫苗的渗透压摩尔浓度检测均值作为对照,进行方差齐性检验及假设检验,比较各疫苗检测均值的差异。结果  麻疹腮腺炎联合减毒活疫苗与对照相比,均值差异无统计学意义（t=1.66,P>0.05）;麻疹减毒活疫苗、风疹减毒活疫苗、水痘减毒活疫苗及流感病毒裂解疫苗与对照相比,均值差异均有统计学意义（Z>1.96,P<0.001）。同种疫苗批间渗透压摩尔浓度较为稳定,变异系数均<3%,变化幅度能控制在90%~110%均值范围内。结论  6种病毒性疫苗渗透压摩尔浓度存在一定差异,但同种疫苗检测值批间稳定性较好,因此,应根据不同疫苗的渗透压摩尔浓度,分别制定质量控制标准。     

新型结核病疫苗研究进展

本文从蛋白质亚单位疫苗、DNA疫苗、重组卡介苗、新型减毒活疫苗和以非致病性分枝杆菌为载体的重组疫苗几方面概括地介绍了目前新型结核病疫苗研制的现状。     

水痘疫苗和巨细胞病毒疫苗近展

本文介绍了水痘疫苗和巨细胞病毒疫苗的研究进展。由于这两种病毒生活周期的复杂性,使疫苗研究进展缓慢。水痘疫苗研究的最大进展还是Oka株减毒活疫苗,它能诱发体液和细胞免疫应答,对水痘（特别是严重水痘）和带状疱疹的预防均有效。巨细胞病毒Towne株减毒活疫苗能有效预防器官移植受者严重巨细胞病毒感染的发生。此外,两种病毒的亚单位疫苗和基因工程载体疫苗的研究也取得不同程度的进展。     

Synthetic biology: impact on the design of innovative vaccines

Conventional vaccine design strategies mainly focus on live-attenuated vaccines, inactivated microorganisms, and subunits thereof comprising purified components or recombinantly expressed proteins, mostly formulated with adjuvants. Although generally very efficient, these approaches are suboptimal or unfeasible for some infectious diseases. Over the past years new technologies to vaccine development have evolved, often utilizing design principles and construction technologies of synthetic biology. The contribution of synthetic biology to vaccine development comprises algorithms for accelerated in silico identification of relevant protein candidates, in silico design of novel immunogens with improved expression, safety and immunogenicity profiles as well as in silico design of (1) nucleic acid based, (2) vectored and (3) live-attenuated vaccines. Furthermore, synthetic biology enables economic and rapid chemical synthesis of DNA encoding the immunogens designed in silico, and their efficient assembly with delivery systems to obtain vectored vaccines. Altogether, synthetic biology can help to develop improved vaccine candidates in considerably less time compared to conventional approaches.     

新型人用狂犬病疫苗研究进展

虽然狂犬病可通过接种狂犬病疫苗来预防,但全球每年仍有超过55 000人因狂犬病死亡。采用现行狂犬病疫苗的多剂接种方案,暴露前疫苗接种对大多数国家来说不具有成本效益,因此有必要开发新型狂犬病疫苗。理想的狂犬病疫苗应与现行的多剂疫苗同样安全,而且单剂接种后就能达到保护性免疫。此综述讨论了处于临床前试验和正在进行临床试验的新型狂犬病疫苗,及其替代现有狂犬病疫苗的潜力。     

Particle-based vaccines for HIV-1 infection

The use of live-attenuated viruses as vaccines has been successful for the control of viral infections. However, the development of an effective vaccine against the human immunodeficiency virus (HIV) has proven to be a challenge. HIV infects cells of the immune system and results in a severe immunodeficiency. In addition, the ability of the virus to adapt to immune pressure and the ability to reside in an integrated form in host cells present hurdles for vaccinologists to overcome. A particle-based vaccine strategy has promise for eliciting high titer, long-lived, immune responses to a diverse number of viral epitopes from different HIV antigens. Live-attenuated viruses are effective at generating both cellular and humoral immunity, however, a live-attenuated vaccine for HIV is problematic. The possibility of a live-attenuated vaccine to revert to a pathogenic form or recombine with a wild-type or defective virus in an infected individual is a drawback to this approach. Therefore, these vaccines are currently only being tested in non-human primate models. Live-attenuated vaccines are effective in stimulating immunity, however challenged animals rarely clear viral infection and the degree of attenuation directly correlates with the protection of animals from disease. Another particle-based vaccine approach for HIV involves the use of virus-like particles (VLPs). VLPs mimic the viral particle without causing an immunodeficiency disease. HIV-like particles (HIV-LP) are defined as self-assembling, non-replicating, nonpathogenic, genomeless particles that are similar in size and conformation to intact virions. A variety of VLPs for both HIV and SIV are currently in pre-clinical and clinical trials. This review focuses on the current knowledge regarding the immunogenicity and safety of particle-based vaccine strategies for HIV-1.     

干扰素在狂犬病疫苗中的佐剂效果研究

目的研究干扰素在狂犬病疫苗中的佐剂效果。方法将人用狂犬病疫苗与干扰素按一定比例混合,制成干扰素佐剂狂犬病疫苗。将干扰素佐剂狂犬病疫苗和无佐剂狂犬病疫苗分别免疫昆明小鼠,并于免疫前和免疫后4,7,14,30,60d时眶静脉采血,用快速免疫荧光灶抑制试验检测小鼠血清中和抗体;同时经腹腔免疫小鼠,第15天时取脾检测淋巴细胞转化率。结果干扰素佐剂狂犬病疫苗可促进免疫细胞增殖。与无佐剂狂犬病疫苗相比,干扰素佐剂狂犬病疫苗诱导产生中和抗体的时间早、滴度高。结论干扰素佐剂狂犬病疫苗具有良好的免疫学效果。     

现代狂犬病疫苗生产用细胞和毒种:现状和前景

对全球狂犬病预防控制的一个主要挑战是不能充分供应廉价优质的狂犬病疫苗。基于神经组织生产狂犬病疫苗的技术早已过时,现代细胞培养技术提供了适当的病毒培养基质,可以获得高滴度病毒和大规模生产高质量的现代狂犬病疫苗。目前人用疫苗仅使用灭活疫苗,用高度适应细胞的稳定的减毒狂犬病病毒生产的疫苗将是未来的理想疫苗。     

Immunizations and pregnancy: An update for pharmacists

ObjectiveTo review the safety of immunizations in pregnancy.Data sourcesPubMed search using the termsvaccine, immunizations, andpregnancy, as well as current national guidelines.Data synthesisImmunizations for women of childbearing age are an integral component of pregnancy planning. Some vaccines are compatible with pregnancy, whereas others, in particular live-attenuated vaccines, are contraindicated because of the theoretical risk to the fetus. The immunizing pharmacist must be aware of updated guidelines regarding the safe and appropriate use of vaccines during pregnancy. Certain routine adult vaccines are contraindicated during pregnancy, including the live-attenuated intranasal influenza, measles–mumps–rubella, varicella, zoster, and human papillomavirus vaccines. The trivalent inactivated influenza vaccine is specifically recommended for all women who are pregnant during influenza season. The hepatitis B, tetanus–diphtheria–acellular pertussis, and several other routine adult and travel vaccines may be administered safely in pregnancy if the patient meets certain risk criteria. Breast-feeding is compatible with all routine adult vaccines. Vaccinia (smallpox) and yellow fever vaccines are cautioned against use except in certain circumstances.ConclusionPharmacists can play an important role in recommending safe and appropriate vaccines before and during pregnancy.     

Vaccine delivery--current trends and future

Since its discovery in 1796 by Edward Jenner, vaccines have been an integral aspect of therapeutics, combating a number of infectious diseases with remarkable success. In recent years, due to rapid advances in proteomics, genomics, biotechnology and immunology and the plethora of knowledge amassed in related fields, it is fair to expect vaccine development to progress at an exponential pace. However, as we march on into the 21st century, we are still struggling in our efforts to eradicate fatal diseases such as AIDS, malaria and hepatitis C due, in part, to the absence of effective vaccines against these diseases. Vaccine development faces major challenges both technologically and economically. Newer vaccines that are stable, economical, require fewer doses and can be administered using needle free systems are a worldwide priority. An ideal theoretical vaccine may not be cogent unless formulated and delivered aptly. Delivery of vaccines via oral, intranasal, transcutaneous and intradermal routes will decrease the risk of needle-borne diseases and may eliminate the need for trained personnel and sterile equipment. Crucial to the success of a vaccine is the delivery strategy that is to be employed. Currently, various techniques involving DNA vaccines, adjuvants, microparticles and transgenic plants are being developed and evaluated. Although, no major breakthrough is in prospect, these systems have potential and will take immunization to a new technological level. This review will focus on the current development of some novel vaccine delivery systems and will explore the non-parenteral routes of vaccine administration.     

以部分疫苗为例分析我国预防用生物制品的改良情况

目的：以百日咳疫苗、人用狂犬病疫苗的改良情况为例,分析监管政策对预防用生物制品技术改良的影响。方法：通过数据分析和文献研究,对我国已批准疫苗的技术改良情况进行分析。结果：技术改良是促进疫苗产业发展的重要手段。结论：监管机构需要通过政策的引导和鼓励促进疫苗的技术改良。