基于结构的流感疫苗设计进展

流感病毒在人类中的传播已有百余年的历史, 然而由于其高度可变的抗原结构, 常规疫苗难以构建持久的保护作用, 开发具备跨亚型保护能力的疫苗成为研究人员面临的挑战。而近十余年发展形成的基于结构的疫苗设计策略有着不同的设计思路, 它注重抗原表位的作用, 将蛋白质结构信息用于抗原设计, 以得到稳定、高效且具有跨亚型保护作用的重组抗原, 为流感疫苗的开发提供了新的突破口。本综述汇总现阶段流感病毒中常见抗原的结构特点与表位特征, 主要针对流感病毒的3种表面蛋白血凝素(HA)、神经氨酸酶(NA)和基质蛋白2(M2), 分别讨论结构疫苗学在这些抗原设计中的应用与进展。     

《当代新疫苗》(第2版)出版

由杨晓明研究员担任主编,6位院士执笔,103位专家学者参加编写的《当代新疫苗》(第2版)由高等教育出版社于2020年1月份正式出版。这是我国疫苗学发展的一件大事,也是一件幸事!本书由陈竺院士作序,赵铠、舒红兵、徐建国、饶子和及王福生5位院士共同推荐。全书分两大部分:第一部分(第1~15章),主要叙述疫苗发展的共性内容,包括疫苗学新技术、黏膜免疫、疫苗佐剂、疫苗载体、DNA疫苗、病毒样颗粒疫苗、联合疫苗、疫苗接种和投递技术、疫苗的临床试验、疫苗生产管理规范和疫苗的安全性评价等。     

黄热病减毒活疫苗的研究进展

黄热病毒疫苗17D (yellow fever attenuated live vaccine-17D,YF-17D)问世于20世纪30年代,至今已有70多年的使用历史,接种人群超过6亿.我国早在20世纪50年代就按照WHO规范开展了黄热病疫苗YF-17D的生产,已有近60年的历史,主要供潜在暴露危险的人群使用;至今我国仍保持年均生产数万份YF-17D疫苗的规模用于计划接种.由于黄热疫苗的安全性高、保护性好,已被国际公认为成功疫苗的典范.新兴的系统疫苗学(systemic vaccinology)是一门综合学科,采用完整的设计、全方位的试验,以及系统地组织和分析各类研究数据,通过总结归纳疫苗引起的生物反应的特征和规律来探求有效疫苗的免疫保护机制的方法.因此近些年,利用系统疫苗学手段研究黄热病毒减毒活疫苗接种后激活的免疫应答类型,将使我们利用YF-17D这一成功的疫苗深入研究免疫系统识别、活化机制,并为以YF-17D为载体的嵌合疫苗研究以及其他病毒性疾病疫苗的设计提供新思路.     

以免疫球蛋白为载体的新型疫苗分子设计

疫苗学（ｖａｃｃｉｎｏｌｏｇｙ）的研究迄今已有２００多年的历年。疫苗的类型也由早期的灭活和减毒活疫苗发展到亚单位疫苗、重组疫苗、载体疫苗、抗独特疫苗等。更有意义的是近年治疗性疫苗（ｔｈｅｒａｐｅｕｔｉｃｖａｃｃｉｎｅｓ）概念的提出及其临床应用，大大拓宽了疫苗学的研究范围，分子生物学新理论、新技术的广泛应用，使得人们摆脱了以完整病原体或其天然结构成分为基础进行疫苗研制的传统观念；以精心选择的抗原片断或抗原表位为目的抗原，经分子设计重构，就有可能获得一结构全新、功能多样的新型预防性或／和治疗性疫苗。…     

颗粒性肽-DNA复合疫苗抗肿瘤免疫的研究

诱导有效的抗肿瘤免疫应答是肿瘤免疫治疗的主要目标 ,由于肽疫苗和DNA疫苗具备较高的安全性和实用性 ,因而成为肿瘤疫苗学领域中发展最为迅速的肿瘤免疫治疗方案之一。但是这两种疫苗形式仍然具有各自的缺点 ,其抗原呈递动力学存在显著差异 ,提示这两种疫苗可能存在互补性。本研究对多肽疫苗和DNA疫苗进行综合 ,设计出新型肽 DNA复合疫苗 ,并以P815A为模式抗原 ,证实了该种新型疫苗激发抗肿瘤免疫的有效性     

中国多表位疫苗设计的HLA-Ⅰ积累表型频率空间预测系统

目的建立HLA-Ⅰ积累表型频率(CPF)的空间预测系统,旨在指导中国疫苗学家设计受HLA限制的多表位疫苗(包括DNA疫苗),并评价或预测根据不同HLA-Ⅰ组合形式设计的多表位疫苗(或DNA疫苗)在中国不同地区的免疫效果。方法通过构建中国境内人群HLA-Ⅰ基因空间数据库,利用“克立格”技术建立CPF空间预测系统。结果根据疫苗设计目的,设计者可利用该系统预测和估计特定地理位置上人群的CPF,包括根据单个HLA座位(HLA-A或HLA-B)上的等位基因而设计的多表位疫苗和根据两个HLA基因座位(HLA-A和HLA-B)上的等位基因而设计的多表位疫苗在特定地理位置上人群的CPF值,从而估计或预测拟研制的或已研制的多表位疫苗在中国不同地理位置上人群中的免疫效果。结论该预测系统可用于：①鉴别任何中国群体的期望CPF百分比,为设计疫苗组分提供依据;②在特定地理位置的人群中,预测限制性表位已知的多表位疫苗的理论免疫应答率;③在特定地理位置的人群中,识别因缺乏HLA-Ⅰ限制性等位基因而不能对表位疫苗产生免疫应答的个体。。     

美试验抗癌新疫苗

美试验抗癌新疫苗据美国报刊最近报道，美国科学家正在试验一种医治癌症的新疗法。纽约的一个癌症研究中心正在对２４例早期转移性前列腺癌患者试用一种新疫苗制剂。该中心的肿瘤疫苗学、生物有机化学和肿瘤抗原免疫化学的三个实验室的研究人员，使合成化学、免疫学和医学...     

柯萨奇B3病毒的纯化及其初步应用

柯萨奇Ｂ组病毒 (ｃｏｘｓａｃｋｉｅｖｉｒｕｓｇｒｏｕｐＢ)是人类病毒性心肌炎的主要病原体 ,其中以ＣＶＢ3最常见[1] 。目前尚无特异性的防治措施 ,研制安全有效的疫苗为当务之急。ＤＮＡ疫苗是目前疫苗学研究的热点。但一般来讲 ,ＤＮＡ疫苗诱导的免疫反应低[2 ,3 ] 。如果没有纯度高、特异性强的抗原 ,低水平的免疫反应很可能会检测不到。我们在柯萨奇病毒ＤＮＡ疫苗的研究工作中就碰到了这个问题。因此 ,制备高纯度的检测特异性免疫反应用抗原即成为该疫苗研究中必须解决的问题。我们应用ＨｅＬａ细胞大量培养ＣＶＢ3,经ＣｓＣｌ密度…     

基于狂犬病病毒载体的基因工程疫苗研究进展

对HIV-1和HCV等重大传染性疾病传统疫苗研制的失败,让科学家们把目光转向开发新型疫苗研制策略。其中之一就是用减毒的重组病毒载体表达外源抗原来免疫,可以保护个体免受相应病原体的暴露威胁。一种新的手段就是从cDNA克隆拯救单股负链RNA病毒,这一技术为弹状病毒科成员用于疫苗载体和生物医学工具打开了一扇窗。     

抗个体独特型抗体疫苗

抗个体独特型抗体疫苗这个名称,乍听起来觉得新鲜且令人费解。因为经典的免疫学关于疫苗的定义是:将微生物接种于动物或组织培养,生长后的收获物经处理或提取微生物的某些组分而制备的具有抗原性的制品。那么,一向作为被动免疫制剂的抗体怎么一跃成为主动免疫用的疫苗呢?这正是本文试图阐明的问题。抗个体独特型抗体疫苗与基因工程疫苗和合成肽疫苗并列,成为现代分子疫苗发展的三大方向。     

Systems immunogenetics of vaccines

Vaccines are the most cost effective public health measure for preventing viral infection and limiting epidemic spread within susceptible populations. However, the efficacy of current protective vaccines is highly variable, particularly in aging populations. In addition, there have been a number of challenges in the development of new vaccines due to a lack of detailed understanding of the immune correlates of protection. To identify the mechanisms underlying the variability of the immune response to vaccines, system-level tools need to be developed that will further our understanding of virus–host interactions and correlates of vaccine efficacy. This will provide critical information for rational vaccine design and allow the development of an analog to the “precision medicine” framework (already acknowledged as a powerful approach in medicine and therapeutics) to be applied to vaccinology.     

Precision medicine in Thailand

Extraordinary advances in high throughput next generation sequencing (NGS) technology and bioinformatics are the main thrust that transforms the current state of healthcare into the era of precision medicine where clinical practice takes individual variability into account. Here, we summarize the current status of the infrastructure we have and the adoption of precision medicine in Thailand in four spheres: rare diseases, oncology, pharmacogenomics, and noncommunicable diseases. Moreover, we provide our perspectives to the future of precision medicine in Thailand, especially the manpower and ethical, legal, and social issues. We believe that with decreasing costs of NGS, increasing ability to interpret the genomic data, a greater number of actionable and available treatments, implementation of precision medicine at the public health level is not a matter of if but when.     

Monitoring the impact of vaccines postlicensure: new challenges, new opportunities

Although vaccines are studied intensively before licensure, insight into important aspects of vaccine performance and the effectiveness of immunization programs and policies can only be detected after vaccines enter widespread use. Now that 17 diseases are targeted for prevention through routine immunizations in the USA, reassessment of the nation's vaccine-preventable disease-monitoring efforts is appropriate. Postlicensure disease monitoring has permitted recognition of indirect protection, vaccine effectiveness of various schedules, duration of protection, health disparities, importation patterns and microbial adaptation. The investments in vaccine research, development and regulatory procedures prelicensure, as well as resources devoted to purchase, distribution and delivery of vaccines after introduction, necessitate strategic efforts to monitor the impact of large-scale use of vaccines on disease over time.     

Challenges for precision public health communication in the era of genomic medicine

Although still in the early stages of development, the advent of fast, high-output, and cost-effective next-generation DNA sequencing technology is moving precision medicine into public health. Before this shift toward next-generation sequencing in public health settings, individual patients met geneticists after showing symptoms and through limited family screening. In the new era of precision public health, everyone is a possible participant in genetic sequencing, simply by being born (newborn screening), by donating blood (biobanking), or through population screening. These initiatives are increasingly offered to individuals throughout their life and more individuals are encountering opportunities to use DNA sequencing. This article raises awareness of these growing areas and calls for different models of public engagement and communication about genomics, including screening asymptomatic populations, obtaining consent for unspecified and unforeseen future uses of genomic data, and managing variants of uncertain significance. Given that such communication challenges loom large, established norms of practice in genomic medicine and research should be reconsidered.     

Exoerythrocytic malaria vaccine development: understanding host-parasite immunobiology underscores strategic success

Malaria imposes an enormous health burden on people living in the tropics and effective control measures are urgently needed. The vast majority of deaths in humans from malaria are caused by one species of the protozoan, Plasmodium falciparum. An efficacious and cost-effective vaccine against this parasite is considered a holy grail of modern molecular medicine. A vaccine that targets liver-stage parasites would prevent infection from reaching the blood and causing clinical disease. Among around 40 known Plasmodium falciparum antigens, only a few are expressed exclusively by mosquito-transmitted sporozoites or infected hepatocytes. Studies in humans have consistently related immune responses to these antigens with resistance to infection or disease, providing a powerful rationale for the development of pre-erythrocytic vaccines. By dissecting the mechanism(s) of immunity to these antigens, we can best evaluate in different delivery systems epitopes associated with protection as components of a focused and coordinated multiantigen malaria vaccine strategy.     

Boosting with poxviruses enhances Mycobacterium bovis BCG efficacy against tuberculosis in guinea pigs

Tuberculosis is rising in the developing world due to poor health care, human immunodeficiency virus type 1 infection, and the low protective efficacy of the Mycobacterium bovis BCG vaccine. A new vaccination strategy that could protect adults in the developing world from tuberculosis could have a huge impact on public health. We show that BCG boosted by poxviruses expressing antigen 85A induced unprecedented 100% protection of guinea pigs from high-dose aerosol challenge with Mycobacterium tuberculosis, suggesting a strategy for enhancing and prolonging the efficacy of BCG.     

Analysis of the relationship between immunogenicity and immunity for viral subunit vaccines

The prevention of viral infection by vaccination relies on stimulating an appropriate immune response in order to reduce the probability with which a virus can establish an infection. Post-vaccination antibody responses have therefore been associated with reducing the probability with which an individual can be infected (i.e., the vaccine's "impact"). Quantifying this relationship is essential in evaluating new vaccines, especially since comparisons between vaccines, and vaccine licensure, may be dependent on antibody responses alone. In this paper two principal questions are identified which need to be addressed in the evaluation of subunit vaccines: i) how do specific antibody levels relate to complete protection from infection or disease and ii) how do antigenic subunits interact in developing protection when combined together in a single vaccine. The aim is to identify explicitly certain assumptions that are frequently made implicitly in the discussion of vaccine action. First, antibody levels are related to levels of protection through a novel statistical analysis of incidence data from a published hepatitis B vaccine trial. The antibody response observed after influenza A virus infection is discussed in relation to the selection of neutralisation escape variants. Finally, by way of example, a theoretical situation is examined and three simple models of subunit vaccine action are constructed in order to describe how antibody levels may be related to population level phenomena such as the elimination of an infection by mass vaccination.     

Immunity to liver stage malaria: considerations for vaccine design

Malaria is the world's deadliest parasitic disease and effective control measures are a public health priority. Most deaths in humans from malaria are caused by one species of the protozoa, Plasmodium falciparum. An efficacious and cost-effective vaccine against this parasite is considered a holy grail of modern molecular medicine. A vaccine that targets liver stage parasites would prevent infection from reaching the blood and causing clinical disease. Among known P. falciparum antigens, liver stage antigen-1 (LSA-1) is the only protein expressed exclusively by infected hepatocytes. Several independent studies in humans have consistently related immune responses to LSA-1 with resistance to infection or disease, providing a powerful rationale for the development of liver stage vaccines. Investigations by ourselves and others aim to dissect the mechanism of cellular immunity to LSA-1 and to evaluate in different delivery systems epitopes associated with protection as components of a multiantigen malaria vaccine. The first clinical trials are already being conducted, the results of which are eagerly awaited.     

Precision health: A pragmatic approach to understanding and addressing key factors in autoimmune diseases

The past decade has witnessed a significant paradigm shift in the clinical approach to autoimmune diseases, lead primarily by initiatives in precision medicine, precision health and precision public health initiatives. An understanding and pragmatic implementation of these approaches require an understanding of the drivers, gaps and limitations of precision medicine. Gaining the trust of the public and patients is paramount but understanding that technologies such as artificial intelligences and machine learning still require context that can only be provided by human input or what is called augmented machine learning. The role of genomics, the microbiome and proteomics, such as autoantibody testing, requires continuing refinement through research and pragmatic approaches to their use in applied precision medicine.     

Cognitive factors in health psychology and behavioral medicine

Research in health psychology and behavioral medicine has increased exponentially over the past three decades. Prevention and control efforts across a variety of diseases have recognized that individual difference factors, belief systems, attitudes, behaviors, and environments can affect an individual's health. This work continues, as there has been no abatement in the rate at which aversive, chronic, and life-threatening diseases continue to affect millions of Americans each year. The purpose of this review is to discuss the influence of cognitive factors on health psychology and behavioral medicine using the cancer literature as an example. The main discussion focuses on the impact of cognitive constructs on behavioral medicine and health psychology in cancer, which appears to be widespread. The article concludes with some implications for future research in the area.