Tuberculosis vaccines: progress and challenges

An effective tuberculosis (TB) vaccine could have a significant impact on the current TB pandemic. The past decade has seen sustained global investment into reaching this goal; currently there are several promising vaccines in clinical trials. Current strategies include the development of an improved bacille Calmette-Guerin (BCG) vaccine to be given at birth and a booster vaccine to be administered after BCG. Here, we describe the current vaccination strategy and review the main issues in novel TB vaccine development. Potential vaccine candidates are evaluated in pre-clinical animal models, and the most promising go into clinical testing; a vaccine candidate is evaluated in at least one model before progressing to early clinical trials. The main challenge in early trials is the lack of a defined correlate of vaccine-induced immune protection. Following this, large efficacy trials are undertaken, which face the daunting challenges of cost, logistics and trial site capacity.     

Tuberculosis vaccines: current status and future prospects

There is an urgent need to develop more effective tuberculosis vaccines as chemotherapy and Bacille Calmette-Guérin (BCG) have failed to control the current epidemic. BCG does have some protective effect in childhood, so using a second vaccine to boost BCG would be the most ethical and logistically feasible strategy. The cost of tuberculosis efficacy trials will be high and return on investment into the development of a tuberculosis vaccine will be low. Incentives such as orphan drug status could encourage industrial interest. As more vaccines enter into early clinical trials, there is an urgent need for the identification of correlates of protection to aid decisions about which vaccines should go forward into efficacy testing. Research efforts that focus on reducing the cost and risk of conducting clinical trials will be of direct benefit to tuberculosis vaccine development.     

DNA vaccines against cytomegalovirus: current progress

The development of a vaccine for the prevention of primary cytomegalovirus (CMV) infection is a major public health priority. Live attenuated virus, recombinant viral vector, recombinant protein and peptide vaccines have been studied as potential vaccine candidates. In recent years, DNA vaccination strategies have been developed for many pathogens, including CMV. This review aims to bring together many aspects of this relatively new vaccine technology as applied to current research into the development of vaccines against CMV.     

HIV vaccines: progress to date

The quest for an effective and safe HIV-1 vaccine has been and still is the aspiration of many scientists and clinicians worldwide. Until recently, the hopes for an effective vaccine were thwarted by the disappointing results and early termination in September 2007 of the STEP study, which saw a subgroup of male vaccine recipients at an increased risk of HIV-1 infection, and the failure of earlier trials of vaccines based on recombinant envelope proteins to provide any level of protection. The results of the STEP study raised important questions in the field of HIV vaccines, including the use of recombinant adenovirus vectors as immunogens, the rationale for the development of T-cell-based vaccines and the development pathway for these vaccines, in terms of assessment of immunogenicity and the challenge models used. The study of neutralizing antibodies has demonstrated that the induction of high-titre, broadly neutralizing antibodies in the majority of recipients is likely to be highly problematic. However, the results of the RV144 Thai trial released in September 2009 have brought new optimism to the field. This study employed envelope-based immunogens delivered as a priming vaccination with a recombinant poxvirus vector and boosting with recombinant proteins. This regimen provided modest protection to HIV-1 infection in a low-risk population. Although the correlates of protection are currently unknown, extensive studies are underway to try to determine these. Neutralizing antibodies were not induced in the RV144 study; however, considerable titres of binding antibodies to HIV-1 viral envelope (Env) were. It is speculated that these antibodies may have provided a means of protection by a mechanism such as antibody-dependent cell-mediated cytotoxicity. In addition, no CD8+ T-cell responses were induced, but robust CD4+ T-cell responses were, and correlates of protection are being sought by analysing the quality of this aspect of the vaccine-induced immune response. The current paradigm for an optimal HIV-1 vaccine is to design immunogens and vaccination protocols that allow the induction of both broadly neutralizing humoral and broadly reactive and effective cell-mediated immunity, to act at sites of possible infection and post-infection, respectively. However, this is challenged by the results of the RV144 trial as neither of these responses were induced but modest protection was observed. Understanding the biology and immunopathology of HIV-1 early following infection, its modes of transmission and the human immune system's response to the virus should aid in the rational design of vaccines of increased efficacy.     

Cell-based influenza vaccines: progress to date

Human vaccines against influenza have been available for almost 60 years and, until recently, were prepared almost entirely from viruses grown in the allantoic cavity of 9- to 11-day-old embryonated chicken eggs. Manufacture involving eggs is not sufficiently flexible to allow vaccine supplies to be rapidly expanded, especially in the face of an impending pandemic. Other problems may arise from the infections of progenitor flocks that adversely affect egg supplies, and from the manufacturing process itself, where breakdowns in sterility can occur from the occasional contamination of large batches of viral allantoic fluid. In addition, egg-grown viruses exhibit differences in antigenicity from viruses isolated in mammalian cell lines from clinical specimens. These concerns and the probable need for greatly expanded manufacturing capability in the future have been brought into focus in recent years by the limited spread of H5N1 avian influenza infections to humans in several Asian countries. Alternative approaches involving the use of accredited anchorage-dependent and -independent preparations of the African Green monkey kidney (Vero), Madin-Darby canine kidney (MDCK) and other cell lines have been pursued by several manufacturers in recent years. Yields comparable with those obtained in embryonated eggs have been achieved. These improvements have occurred in parallel with newer technologies that allow the growth of cells in newer synthetic media that do not contain animal serum, in order to allay the concerns of regulators about the potential for spread of transmissible spongiform encephalopathies.     

Hepatitis E vaccines: progress and prospects

Hepatitis E accounts for the major part of enterally transmitted non-A, non-B hepatitis worldwide. Its agent, the hepatitis E virus (HEV), is a small, single-stranded RNA virus. Only one serotype of HEV is recognised. Infection results in protective immunity with long-lived neutralising antibodies. In developing countries with poor sanitary conditions and high population density, hepatitis E causes water-borne epidemics with substantial mortality rates in pregnant women. In addition, more than 50% of cases of acute hepatic failure and sporadic acute hepatitis are due to hepatitis E. The overall prevalence rates of antibodies to the HEV in populations native to these areas rarely exceed 25%. Hence, many individuals remain susceptible to hepatitis E infection, making hepatitis E an important public health concern.In this context, the development of an HEV vaccine is warranted. Because HEV does not grow adequately in cell cultures the development of a vaccine based on inactivated or attenuated whole-virus particles is not feasible. HEV vaccines currently under study are based on recombinant proteins derived from immunogenic parts of the HEV capsid gene. Other approaches such as DNA-based vaccines or transgenic tomatoes have also been developed. Several recombinant protein-based vaccines elicited neutralising antibodies and protective immunity in vaccinated non-human primates. One such vaccine has passed phase I trial and is currently under further evaluation in field trials. Even so, several questions remain to be answered before vaccination programmes could be implemented.     

肠道细菌性疫苗研究进展

人肠道致病菌具有高度传染性，可引起多种疾病。目前已有多种肠道细菌灭活疫苗和减毒活疫苗通过安全性评价上市；重组蛋白疫苗、结合疫苗和亚单位疫苗等新型疫苗的研究已获得较好的结果。此文对人肠道致病菌及其相关新疫苗的研究进展做一综述。     

肿瘤疫苗的研究进展

恶性肿瘤是威胁人类健康的严重疾病,目前尚无完全有效的治疗方法.随着医学和生物技术的发展,肿瘤治疗方法已呈现多样化,肿瘤疫苗作为其中一种治疗策略正日益受到人们的关注.此文就肿瘤疫苗研究进展作一综述.     

肿瘤疫苗的研究进展

恶性肿瘤是威胁人类健康的严重疾病,目前尚无完全有效的治疗方法.随着医学和生物技术的发展,肿瘤治疗方法已呈现多样化,肿瘤疫苗作为其中一种治疗策略正日益受到人们的关注.此文就肿瘤疫苗研究进展作一综述.     

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.     

肺炎链球菌疫苗研究进展

肺炎链球菌疫苗接种是抵抗肺炎链球菌病的最主要策略之一.此文阐述了后7价肺炎链球菌结合疫苗接种时代的肺炎链球菌病的临床和流行特征、新批准的2种肺炎链球菌结合疫苗的应用以及基于蛋白的肺炎链球菌疫苗的研发现状.     

流感疫苗的研究进展

流感是我国每年秋冬季常见的呼吸道传染病。接种疫苗是防控流感最为有效的措施。目前,多种类型的流感疫苗正在研发之中或已上市,同时,流感疫苗规模化生产的基质也逐渐从鸡胚转为哺乳动物细胞。此文介绍了流感疫苗的研究进展以及疫苗生产基质的变迁。     

Lactococcus lactis-based vaccines: current status and future perspectives

Lactococcus lactis offers significant potential as a platform for the delivery of vaccines especially via mucosal routes of administration. The organism has an established history of safe use in the food industry and is highly amenable to genetic manipulation, with many systems available for efficient production of secreted and surface-expressed proteins. Here we describe the benefits of using this organism as a vaccine delivery platform and outline how L. lactis based antigen delivery may be improved. Finally we discuss the safe use of L. lactis vectors and outline the potential for use of biological containment systems and killed lactococcal preparations.     

脑心肌炎病毒疫苗研究进展

脑心肌炎病毒是一种人畜共患病病毒,其宿主范围很广,可引起动物脑心肌炎,亦可感染人类.目前,脑心肌炎病毒疫苗的研究正在日益受到重视.此文就脑心肌炎病毒疫苗研究进展进行综述.

Abstract：

Encephalomyocarditis virus(EMCV) is a kind of zoonotic virus, and has a wide range of hosts. EMCV can cause encephalomyocarditis in animal, and human also can be infected with EMCV. At present, people gradually pay more attention to EMCV vaccine development. This article reviews research progress in EMCV vaccines.     

肠道病毒71型疫苗研究进展

 肠道病毒71型（enterovirus 71,EV71）是引起手足口病（hand, foot and mouth disease,HFMD）的主要病原体之一,HFMD可并发神经系统疾病,甚至导致死亡。对于EV71感染,目前尚无有效的治疗药物和措施,因此研制有效的疫苗是控制EV71流行的最佳方法。此文就EV71疫苗的研究进展进行综述。     

幽门螺杆菌疫苗研究进展

幽门螺杆菌感染在全世界广泛存在,能引起多种胃部疾病,包括胃癌.尽管抗生素治疗有效,但是人们一致认为幽门螺杆菌疫苗可能是控制幽门螺杆菌感染的最佳方法.有效的幽门螺杆菌疫苗策略可显著增进全世界人群的健康.此文就幽门螺杆菌疫苗的保护性抗原、佐剂、动物模型、免疫机制的研究进展进行综述.     

基于碳水化合物的抗肿瘤疫苗研发进展

糖生物学研究新技术的发展为碳水化合物疫苗的研究提供了新思路。从理论上讲,各种类型细胞的表面抗原决定簇都可用于疫苗的开发。近年来已经研制成多种碳水化合物疫苗,此文主要介绍抗肿瘤碳水化合物疫苗的研究新进展。