衣原体mRNA疫苗的研发对策与展望北大核心CSCD

衣原体是一类专性胞内寄生、多宿主病原体,可感染眼部粘膜、呼吸道、泌尿生殖道等,引起人类与动物多种感染性疾病及并发症。然而衣原体常呈隐匿性感染,潜伏期长,临床上仅呈现轻微症状甚至无症状,抗生素治疗后常出现感染反复持续、迁延难愈现象,对人类公共卫生和畜牧业造成严重威胁。因此,研发安全高效的衣原体疫苗是防治衣原体感染的重要手段。mRNA疫苗是近年新兴的疫苗,在抗病毒、抗传染性疾病病原体方面应用广泛。过去几十年疫苗的研究显示,与全菌疫苗、亚单位疫苗以及DNA疫苗相比,mRNA疫苗不仅在安全性、免疫性、灵活性等方面更具优势,在传染病的预防方面也具有强大潜力。我们通过总结近年来衣原体疫苗以及mRNA疫苗的相关研究和重要发现,系统介绍合理研发衣原体mRNA疫苗过程中衣原体抗原选择、佐剂选择、抗原递送及免疫途径等重要环节及注意事项,为研发安全有效的衣原体mRNA理想疫苗提供设计思路和理论依据。     

鹦鹉热衣原体基因工程亚单位疫苗免疫羊抗体产生动力曲线

目的观察鹦鹉热衣原体基因工程亚单位疫苗免疫羊后产生的动力学曲线。方法用不同剂量鹦鹉热衣原体主要外膜蛋白基因工程亚单位疫苗免疫绵羊,免疫前及免疫后不同时间采血检测抗体情况,观察绵羊抗体的产生和变化水平。结果免疫剂量为0.5mg/只颈部肌肉多点注射,具有良好的免疫效果。结论鹦鹉热衣原体基因工程亚单位疫苗免疫剂量为0.5mg/只颈部肌肉多点注射,在绵羊整个妊娠期内具有保护作用。     

衣原体纳米疫苗的研究进展

衣原体疫苗接种的最终目的是刺激机体体液免疫、细胞免疫及黏膜免疫应答的有机结合,以发挥抗感染保护作用、减少炎症病理的形成。衣原体抗原成分单独接种或与佐剂联合应用均不能全面激发机体的免疫应答。纳米粒子因具有降低毒副作用、靶向输送、缓释、避免被酶降解、提高活性和稳定性等独特优势,为衣原体疫苗设计提供了新策略。应用于医学领域的纳米材料种类繁多,衣原体纳米疫苗已取得一定程度的进展,本文主要对纳米粒子脂质体和多聚体微粒在衣原体疫苗中的研究进展作简要概述。     

日本血吸虫病核酸疫苗研究进展

血吸虫病是严重危害人类健康的寄生虫病,寻找新的杀虫药物和开发研制有效抗血吸虫疫苗已成为刻不容缓的工作。随着现代分子生物学及免疫学的发展,血吸虫病疫苗已由减毒活疫苗、基因重组抗原疫苗发展到核酸疫苗等阶段[1-2]。疫苗是20世纪最重要的公共卫生成就之一[3]。传统的疫苗研究策略是模拟自然感染,成功的疫苗多依赖于中和抗体的产生;虽然减毒活疫苗的免疫保护作用效果显著,但缺乏足够的虫源,且多种抗原成分不一定全部产生保护力,甚至可能导致免疫性病变或免疫抑制。基因重组抗原疫苗应用安全,但只能引起体液免疫,且蛋白的提取纯化步骤…     

刚地弓形虫复合基因疫苗、混合疫苗及多表位疫苗研究进展

有效的疫苗免疫是预防弓形虫病的最理想方法.当前弓形虫疫苗的研制虽然取得了一些进展,但是单价疫苗的免疫效果并不理想.寻找更有效的候选抗原基因和合适的载体及研究多种抗原基因的优化组合将是今后弓形虫疫苗研究的主要方向.该文就弓形虫复合基因疫苗、混合疫苗及多表位疫苗的研究进展进行综述.     

布鲁氏菌病疫苗研究进展

使用疫苗免疫是防控布氏菌病(简称布病)的重要措施之一,但对人群使用疫苗免疫一直存有争议,世界上主要是俄罗斯(前苏联)和中国使用19-BA疫苗和104M疫苗对布病高危人群进行免疫.对于动物布病,早期曾使用灭活疫苗进行免疫,目前主要使用S19,Rev.1,RB51,S2和M5等弱毒活疫苗,其中Rev.1和S19是预防小反刍动物和奶牛布病最有效的疫苗,其它疫苗的使用也比较广泛.初步研究表明基因工程疫苗等新型布病疫苗具有良好的应用前景,但尚未被官方认可用于人和动物的布病免疫.特对人布病疫苗和动物布病疫苗进行介绍,并对基因工程疫苗以及其它新型布病疫苗的最新研究进展进行概述.     

应用H4-IC31疫苗或BCG复种预防结核分枝杆菌感染

<正>背景:结核分枝杆菌近期感染可发展成结核病,目前结核病仍是全球传染病中的头号杀手。疫苗可有效预防青少年感染结核病,并通过阻断传播,对敏感和耐药菌株的控制有重要影响。因为缺乏有效的临床前模型和人类免疫相关的保护,目前新疫苗的开发受到阻碍。H4-IC31是一种候选的亚单位疫苗,由重组融合蛋白(H4)和IC31佐剂组成,通过Toll样受体9(TLR9)信号传导,含有分枝杆菌抗原     

基于流感病毒M2蛋白的通用疫苗研究进展

流感疫苗在不同亚型间的交叉保护力较差,且存在有抗原漂移和转换现象,严重影响了疫苗的免疫效果,甚至导致疫苗免疫失败。这就需要开发一种能对各种不同亚型流感病毒均安全有效通用疫苗。本文就针对流感病毒M2蛋白的通用疫苗做一综述。     

用于控制寄生虫病的疫苗及其实用性和持效性

开发一种寄生虫疫苗的成功不仅取决于疫苗本身的研制而且依赖于有效的免疫计划,否则所开发的疫苗并不一定有利于公众健康。作者认为须全面了解寄生虫病的流行病学特征、疫苗供应系统及其成本和效益。 多数病毒、细菌和原虫疫苗的设计必须考虑病原体基础复制率(R_0)的宿主初次感染的年龄。作者指出高度的人群免疫决定于三个因素,即R_0值、疫苗的有效性和易感人群中获得免疫接种者的比例。R_0值低的病原     

禽流感疫苗研究进展

禽流感是一种禽类的烈性传染病,在世界范围内广泛流传,严重威胁着养禽业.尤其是高致病性禽流感的流行,病死率极高,常常使国家和人民蒙受巨大的经济损失.禽流感的传染性极强,并可跨物种进行传播,禽流感作为一种全新的病种,已成为人类健康和生命的严重威胁,而面对禽流感病毒的侵害,人类自身却毫无免疫防护,所以必须加强禽流感的预防.由于禽流感病毒广泛存在于各种禽类和野生鸟类体内,因此禽流感的控制是一项长期艰巨的任务,疫苗的开发和使用是应对这项艰巨任务最实际、最有效和最经济的手段.理想的疫苗应该是在具备良好的安全性的前提下,不仅能够调动机体的体液免疫,产生病毒中和抗体,更能够充分调动机体的细胞免疫来充分发挥病毒清除机制.     

Chlamydia trachomatis: the role of cellular and humoral immune mechanisms in the development of blindness

Ocular infection with Chlamydia trachomatis leading to trachoma is the commonest cause of treatable blindness worldwide. Although effectively controlled by improved sanitation, a chlamydial vaccine may prove a more cost-effective method of protection against this disease in the medium term. The development of vaccines against Chlamydia trachomatis has been hampered by a lack of understanding of the immune responses leading to protection or pathology, particularly in humans. Although a strong cell-mediated immune response (T helper lymphocyte type 1) is almost certainly necessary to resolve intracellular chlamydial infection, a humoral (T helper lymphocyte type 2) response may protect against colonization and limit immunopathological events. Recent studies addressing this potential conflict are reviewed.     

Chlamydial genomics and vaccine antigen discovery

Vaccine development for Chlamydia species has progressed on several research fronts, including knowledge of the components of the immune response required for immunity and resolution of infection as well as effective modes of delivery. The antigens required to elicit protective immune responses have not been identified. The full biologic potential for Chlamydia trachomatis and Chlamydia pneumoniae was exposed by the completion of the genome sequence for each organism. This knowledge will aid vaccine antigen discovery by facilitating the identification, testing, and evaluation of antigens by way of vaccine delivery approaches that elicit protective immunity.     

Progress in the development of preventive and therapeutic vaccines for hepatitis C virus

Hepatitis C virus (HCV) is a blood borne disease estimated to chronically infect 3% of the worlds' population causing significant morbidity and mortality. Current medical therapy is curative in approximately 50% of patients. While recent treatment advances of genotype 1 infection using directly acting antiviral agents (DAAs) are encouraging, there is still a need to develop vaccine strategies capable of preventing infection. Moreover, vaccines may also be used in future in combination with DAAs enabling interferon-free treatment regimens. Viral and host specific factors contribute to viral evasion and present important impediments to vaccine development. Both, innate and adaptive immune responses are of major importance for the control of HCV infection. However, HCV has evolved ways of evading the host's immune response in order to establish persistent infection. For example, HCV inhibits intracellular interferon signalling pathways, impairs the activation of dendritic cells, CD8(+) and CD4(+) T cell responses, induces a state of T-cell exhaustion and selects escape variants with mutations CD8(+) T cell epitopes. An effective vaccine will need to produce strong and broadly cross-reactive CD4(+), CD8(+) T cell and neutralising antibody (NAb) responses to be successful in preventing or clearing HCV. Vaccines in clinical trials now include recombinant proteins, synthetic peptides, virosome based vaccines, tarmogens, modified vaccinia Ankara based vaccines, and DNA based vaccines. Several preclinical vaccine strategies are also under development and include recombinant adenoviral vaccines, virus like particles, and synthetic peptide vaccines. This paper will review the vaccines strategies employed, their success to date and future directions of vaccine design.     

Vaccines for bacterial sexually transmitted infections: a realistic goal?

Bacterial infections of the genital tract (gonorrhea, chlamydia, chancroid, syphilis) are common and cause significant morbidity. Their importance is heightened by recent appreciation of their roles in facilitation of transmission of the human immunodeficiency virus (HIV). Each is capable of causing repeated infections, suggesting lack of permanent broadly effective immunity. An effective vaccine has yet to be developed for any of these diseases. Rapid progress in understanding the molecular basis for pathogenesis of infection, including mechanisms for escape from otherwise effective immune surveillance and mechanisms for causing injury to host cells, has stimulated renewed efforts to make vaccines for some of these infections. Progress has been greatest for Neisseria gonorrhoeae and Chlamydia trachomatis. Present emphasis is on the major or principal outer membrane proteins of N. gonorrhoeae and C. trachomatis, based on evidence for neutralizing antibodies directed against surface-exposed variable domains of each of these proteins. Other surface-exposed proteins, including the iron-repressible transferrin receptor in gonococci and certain heat-shock proteins in chlamydia, also may be targets for vaccines. Although much remains to be learned, cautious optimism is warranted.     

Efficacy of SIV/deltaB670 glycoprotein-enriched and glycoprotein-depleted subunit vaccines in protecting against infection and disease in rhesus monkeys

Immunization with an inactivated whole-virus vaccine is highly effective in preventing lentivirus infection. The viral protein(s) essential to the induction of protective responses, however, have not been identified. To define the role of virion components in the induction of protective immunity, we evaluated the efficacy of glycoprotein-enriched and glycoprotein-depleted simian immunodeficiency virus (SIV) subunit vaccines prepared by lentil-lectin affinity chromatography of gradient-purified virions using the immunization and challenge regimen previously found successful with an inactivated whole-virus vaccine. Infection was determined by successful recovery of virus, the induction of SIV-specific antibody responses, and infection of naive recipients by inoculation with lymph-node-derived lymphocytes from the vaccinates. Immunization with the glycoprotein-enriched preparation prevented infection in two out of four monkeys, whereas the glycoprotein-depleted vaccine failed to prevent infection in all four vaccinates tested. However, the glycoprotein-depleted vaccine appeared to moderate the progression of SIV-induced disease compared with non-immunized infected control monkeys inoculated with the same challenge dose. These data suggest that subunit vaccines containing sufficient quantities of viral glycoproteins can protect against SIV infection, whereas subunit vaccines composed predominantly of viral core proteins cannot. The development of effective vaccines against HIV infection should include studies on the optimum presentation of the viral envelope glycoproteins to produce long-term broadly protective immune responses.     

Poor response to HBV vaccination and strategies to enhance immunogenicity

Abstract   Hepatitis B vaccination has been proved to be effective in preventing acute and chronic hepatitis B virus (HBV) infection, fulminant hepatitis, and hepatocellular carcinoma. Approximately 5 to 15% of infants and at least 5 to 10% of most healthy adult population failed to produce protective levels of antibodies to HBV vaccination.
The main causes of poor response to HBV vaccination includes intrauterine infection, vaccine escape mutants, genetic hypo-or non-responsiveness to hepatitis B surface antigen (HBsAg) and immune compromised host.
Strategies to enhance immunogenicity to HBV vaccination are as the following: (1) overcome intrauterine or perinatal transmission by antiviral therapy for high risk pregnant women during last trimester, or immediately after birth with HBV hyperimmune globulin for the neonates; (2) higher dosage or more doses of HBV vaccine; (3) better vaccines ; (4) enhance host immune status; (5) better compliance of the vaccines.
In conclusion, current hepatitis B vaccination has been proved to be effective in controlling acute and chronic HBV infection and its complication. Yet further efforts to improve its efficacy generally and in high risk subjects and in immune compromised hosts are needed.     

Vaccines to prevent transmission of HIV-1 via breastmilk: scientific and logistical priorities

Mother-to-child transmission (MTCT) of HIV-1 is the major mode of paediatric infection. The rapidly increasing incidence of MTCT worldwide has resulted in an urgent need for preventive strategies. Antiretroviral regimens can prevent intrapartum HIV transmission; however, these regimens do not prevent HIV transmission through breastfeeding. Furthermore, children who escape MTCT are again at risk of infection when they become sexually active as adolescents. An infant vaccine regimen, begun at birth, would hence be a more attractive strategy and might also provide the basis for lifetime protection. Unique features of MTCT and paediatric HIV disease could be helpful in understanding correlates of immune protection and could facilitate rapid assessment of vaccine efficacy. Thus, there is compelling rationale to develop safe, effective HIV vaccines for use in infants and children. Here, we discuss the scientific and logistical challenges for the development of paediatric HIV vaccines; available vaccines and completed or planned paediatric vaccine trials are also discussed.     

Influenza Vaccines: A Moving Interdisciplinary Field

Vaccination is by far the most effective way of preventing morbidity and mortality due to infection of the upper respiratory tract by influenza virus. Current vaccines require yearly vaccine updates as the influenza virus can escape vaccine-induced humoral immunity due to the antigenic variability of its surface antigens. In case of a pandemic, new vaccines become available too late with current vaccine practices. New technologies that allow faster production of vaccine seed strains in combination with alternative production platforms and vaccine formulations may shorten the time gap between emergence of a new influenza virus and a vaccine becoming available. Adjuvants may allow antigen-sparing, allowing more people to be vaccinated with current vaccine production capacity. Adjuvants and universal vaccines can target immune responses to more conserved influenza epitopes, which eventually will result in broader protection for a longer time. In addition, further immunological studies are needed to gain insights in the immune features that contribute to protection from influenza-related disease and mortality, allowing redefinition of correlates of protection beyond virus neutralization in vitro.     

结核病黏膜疫苗的研究进展北大核心CSCD

呼吸道黏膜免疫是机体抵御结核分枝杆菌(Mycobacterium tuberculosis,MTB)感染的第一道防线,是重要的抗MTB感染的保护性免疫,如何通过黏膜免疫,诱导黏膜免疫系统产生抗MTB感染的特异性免疫,是目前结核病疫苗研究的新方向。本文基于近年来结核病黏膜疫苗的研究,总结了不同类型疫苗的特点、黏膜免疫后的免疫学特性和免疫保护效果,展望了未来结核病黏膜疫苗的研究方向,希望能够对研发更加高效的结核病黏膜疫苗有所启示。     

Progress towards an AIDS mucosal vaccine: an overview

The mucosal immune system acts as a first line of defense against infection caused by luminal pathogens. Because HIV is transmitted primarily via mucosal-associated tissues, particularly with sexual transmission, understanding antiviral immunity present at these sites is important. HIV infection results in depletion of gut-associated lymphoid tissue (GALT) and in this sense can be considered to be a disease of the mucosal immune system. A stumbling block for efforts to develop a vaccine against this disease has been the escape of vaccine-induced neutralizing antibodies and cytotoxic T lymphocytes (CTLs) at mucosal compartments and the resulting viral spread. To avoid these problems, the ideal mucosal vaccine would induce HIV-specific secretory IgA (S-IgA) and mucosal CD8(+) CTL as a first line of defense at a very early stage of HIV infection, before the virus can seed into the secondary lymphoid organs in mucosal and systemic tissues. In this review, we provide an overview of mucosal vaccine concepts and vaccination strategies that have been proposed for the development of an HIV mucosal vaccine, including live recombinant vaccines, peptide-based vaccines, virus-like particles (VLP), subunit vaccines and DNA vaccines.