关注女性生殖道HPV持续性感染

高危型人乳头状瘤病毒（HPV）感染只有持续了一定时间才可能导致宫颈病变乃至宫颈癌。宫颈的HPV感染非常常见,大多数感染者在感染一段时间后可清除HPV,也有些人成为持续性感染者,具有发生高级别宫颈上皮内病变的风险,其中少数进展为浸润癌。有些因素增加了持续性感染的风险,如年龄、多个性伴侣、生殖道同时伴有其他病毒感染、多次分娩（＞3次）和免疫力低下等。HPV感染后的清除机制尚未完全明了,有证据表明宿主的免疫状态及HPV诱导的免疫逃逸与HPV持续性感染有关,免疫细胞及细胞因子起到重要作用。     

EV71感染与固有免疫应答相互作用关系的研究进展

肠道病毒71型（enterovirus 71,EV71）是引起手足口病的主要病原体之一,可引起严重并发症,致残率及病死率较高,是严重危害婴幼儿健康的重大公共卫生问题之一。EV71感染后,宿主启动固有免疫应答抵御感染,而病毒则通过一系列机制逃逸固有免疫的抑制和清除,二者之间存在着博弈关系,两者斗争的结果与EV71感染所致手足口病的病程和结局密切相关。本文就近年来EV71感染与固有免疫应答之间相互作用关系的研究进行综述,旨在为后续研究的深入开展和新型疫苗、药物的研发提供线索和思路。     

慢性乙型肝炎病毒持续感染的免疫机制

HBV为了在患者体内持续存在,它们必须逃避宿主的免疫应答,因此了解HBV引起的慢性肝炎的自然进程和其特点及HBV逃逸机体免疫监视的可能机制,对掌握其致病机制十分关键,可为慢性HBV感染患者的临床治疗提供指导。     

乙型肝炎病毒基因变异与免疫逃逸的研究进展

HBV感染机体后,为了达到长期在宿主体内存在的目的,在机体的免疫压力、药物和其他因素的作用下可发生基因变异,来逃避宿主的免疫监视和清除,不同读码框的不同幕因变异导致免疫逃逸的机制也不相同.此文就HBV不同读码框的基因变异与免疫逃逸的关系进行综述.     

细胞免疫应答与丙型肝炎病毒感染慢性化

HCV感染是导致慢性肝脏疾病的主要病因之一.HCV在感染个体中表现出极高频率的病毒持续性,具有逃逸免疫识别和破坏宿主免疫应答的能力.目前研究认为,细胞免疫对HCV的清除起重要作用,而HCV慢性感染者有不同程度的细胞免疫应答异常.此文对细胞免疫应答与HCV感染及慢性化的可能机制作了综述.     

尿路致病性大肠杆菌感染的免疫应答与炎症反应

尿路致病性大肠杆菌(UPEC)所致的泌尿系感染临床表现是不同的,这不仅与菌株的毒力因子相关,而且与宿主的免疫应答密切相关,文中综述了近期UPEC感染的免疫应答和炎症反应机制的研究进展。     

HIV-1急性感染期的免疫应答特征

HIV-1感染早期的生物学特征及免疫学应答可能是决定艾滋病病程的一个重要因素.近来有研究发现初始有效的免疫应答可驱动病毒逃逸突变的产生,这使得人们对抵御病毒传播的早期免疫应答和急性期病毒血症的控制有了进一步的认识.强烈的固有免疫应答和获得性免疫应答在感染后即可发生,但对于清除病毒却为时已晚.此文讨论了近年来关于HIV-I感染早期免疫应答动力学和特征方面的研究及其对研制有效预防性疫苗的意义.     

丙型肝炎病毒基因变异与免疫

有关丙型肝炎病毒(HCV)持续性感染和发生免疫逃逸的机制至今尚不清楚,但病毒基因组的高度变异性可能是重要原因。本文就HCV基因变异、基因型、准种特性及变异与宿主免疫之间的关系作一综述。     

人乳头瘤病毒免疫逃避研究进展

人乳头瘤病毒感染后可引起感染部位疣、癌等病变。绝大多数感染者会在4～20个月内清除体内的人乳头瘤病毒（human papillomavirus,HPV）,少部分感染者体内将会有病毒持续存在并可能导致癌前损伤及癌变。机体不能成功清除HPV及感染的细胞,是宿主和病毒等多因素共同作用的结果,其中宿主免疫状态对于HPV转归结局的影响尤为重要。HPV逃避宿主免疫攻击引发的病毒清除障碍是HPV持续感染的关键。     

丙型肝炎病毒基因变异与免疫

有关丙型肝炎病毒（ＨＣＶ）持续性感染和发生免疫逃逸的机制至今尚不清楚，但病毒基因组的高度变异性可能是重要原因，本文就ＨＣＶ基因变异，基因型，准种特性及变异与宿主免疫之间的关系作一综述。     

Aerosol delivery of virus-like particles to the genital tract induces local and systemic antibody responses

The induction of mucosal immune responses in the genital tract may be important for increasing the effectiveness of vaccines for sexually transmitted infections (STIs). In this study, we asked whether direct immunization of the mouse genital tract with a non-replicating virus-like particle (VLP)-based vaccine could induce local mucosal as well as systemic antibody responses. Using VLPs derived from two bacteriophages, Qβ and PP7, and from a mammalian virus that normally infects the genital tract, human papillomavirus (HPV), we show that intravaginal aerosol administration of VLPs can induce high titer IgG and IgA antibodies in the female genital tract as well as IgG in the sera. Using a mouse model for HPV infection, we show that intravaginal immunization with either HPV type 16 VLPs or with PP7 bacteriophage VLPs displaying a peptide derived from the HPV minor capsid protein L2 could protect mice from genital infection with an HPV16 pseudovirus. These results provide a general method for inducing genital mucosal and systemic antibody responses using VLP-based immunogens.     

细胞毒性T细胞表位在人乳头瘤病毒疫苗研究中的意义及进展

人乳头瘤病毒(human papilloma virus,HPV)选择性感染皮肤或黏膜上皮细胞,局部形成增生性病变,甚至诱发恶性肿瘤,而以CTL为特征的细胞免疫对抑制HPV感染引起的机体损伤具至关重要的作用。在抗原结构和功能研究中,由CTL识别的抗原决定簇被确定,使含有CTL表位的疫苗取得了长足进展。     

Herd immunity effect of the HPV vaccination program in Australia under different assumptions regarding natural immunity against re-infection

Deterministic dynamic compartmental transmission models (DDCTMs) of human papillomavirus (HPV) transmission have been used in a number of studies to estimate the potential impact of HPV vaccination programs. In most cases, the models were built under the assumption that an individual who cleared HPV infection develops (life-long) natural immunity against re-infection with the same HPV type (this is known as SIR scenario). This assumption was also made by two Australian modelling studies evaluating the impact of the National HPV Vaccination Program to assist in the health-economic assessment of male vaccination. An alternative view denying natural immunity after clearance (SIS scenario) was only presented in one study, although neither scenario has been supported by strong evidence. Some recent findings, however, provide arguments in favour of SIS.     

宫颈病变患者阴道局部免疫功能的变化与HPV转归的研究进展

持续的人乳头状瘤病毒（HPV）感染是发生宫颈病变的高危因素。在宫颈HPV感染及宫颈病变发生、发展的过程中,阴道局部的体液免疫及细胞免疫是抵抗病毒感染及病变发生的第一道防线,也与肿瘤的发生、发展有着密切的联系。其中细胞免疫发挥着主要的抗病毒及减少病毒复制作用,同时体液免疫也在这个过程中发挥着重要的协同作用。在HPV感染引起的宫颈病变治疗前后,阴道局部的体液免疫及细胞免疫功能也会同时发生变化,免疫功能的变化提示预后以及HPV转归的情况,在宫颈病变发生前或发生过程中,有目的地增强患者的免疫功能是否能为疾病的预防及治愈起到指导作用是研究的重要方向。综述HPV感染引起的宫颈病变患者治疗后免疫功能的变化与HPV转归的最新研究进展。     

Vaccine development: From concept to early clinical testing

In the 21st century, an array of microbiological and molecular allow antigens for new vaccines to be specifically identified, designed, produced and delivered with the aim of optimising the induction of a protective immune response against a well-defined immunogen. New knowledge about the functioning of the immune system and host pathogen interactions has stimulated the rational design of vaccines. The design toolbox includes vaccines made from whole pathogens, protein subunits, polysaccharides, pathogen-like particles, use of viral/bacterial vectors, plus adjuvants and conjugation technology to increase and broaden the immune response. Processes such as recombinant DNA technology can simplify the complexity of manufacturing and facilitate consistent production of large quantities of antigen. Any new vaccine development is greatly enhanced by, and requires integration of information concerning:1. Pathogen life-cycle & epidemiology. Knowledge of pathogen structure, route of entry, interaction with cellular receptors, subsequent replication sites and disease-causing mechanisms are all important to identify antigens suitable for disease prevention. The demographics of infection, specific risk groups and age-specific infection rates determine which population to immunise, and at what age.2. Immune control & escape. Interactions between the host and pathogen are explored, with determination of the relative importance of antibodies, T-cells of different types and innate immunity, immune escape strategies during infection, and possible immune correlates of protection. This information guides identification and selection of antigen and the specific immune response required for protection.3. Antigen selection & vaccine formulation. The selected antigen is formulated to remain suitably immunogenic and stable over time, induce an immune response that is likely to be protective, plus be amenable to eventual scale-up to commercial production.4. Vaccine preclinical & clinical testing. The candidate vaccine must be tested for immunogenicity, safety and efficacy in preclinical and appropriately designed clinical trials.This review considers these processes using examples of differing pathogenic challenges, including human papillomavirus, malaria, and ebola.     

Human papillomavirus 16 L1-E7 chimeric virus like particles show prophylactic and therapeutic efficacy in murine model of cervical cancer

Cervical cancer is found to be associated with human papillomavirus (HPV) infection, with HPV16 being the most prevalent. An effective vaccine against HPV can thus, be instrumental in controlling cervical cancer. An ideal HPV vaccine should aim to generate both humoral immune response to prevent new infection as well as cell-mediated immunity to eliminate established infection. In this study, we have generated a potential preventive and therapeutic candidate vaccine against HPV16. We expressed and purified recombinant HPV16 L1(ΔN26)-E7(ΔC38) protein in E. coli which was assembled into chimeric virus like particles (CVLPs) in vitro. These CVLPs were able to induce neutralizing antibodies and trigger cell-mediated immune response, in murine model of cervical cancer, exhibiting antitumor efficacy. Hence, this study has aimed to provide a vaccine candidate possessing both, prophylactic and therapeutic efficacy against HPV16 associated cervical cancer.     

人乳头瘤病毒疫苗

生殖道人乳头瘤病毒感染被认为是最普遍的性传播疾病.人乳头瘤病毒的状况能够预测鳞状上皮内病变将来的进展,高危型人乳头瘤病毒与肛门及生殖器区域的癌前病变及恶性病变有关.持续人乳头瘤病毒感染是宫颈上皮癌变的重要危险因子.预防性疫苗旨在增强免疫应答,以预防感染和防止临床疾病的发展.治疗性疫苗适用于已经出现人乳头瘤病毒感染的个体.发展中国家通过安全有效的疫苗来预防宫颈癌会得到的巨大受益,儿科给药也许是较好的解决方式.     

Immune responses to human papillomavirus

The immune system uses innate and adaptive immunity to recognize and combat foreign agents that invade the body, but these methods are sometimes ineffective against human papillomavirus (HPV). HPV has several mechanisms for avoiding the immune system. HPV infects, and multiplies in keratinocytes, which are distant from immune centers and have a naturally short lifespan. The naturally short life cycle of the keratinocyte circumvents the need for the virus to destroy the cell, which would trigger inflammation and immune response. In addition, HPV downregulates the expression of interferon genes. Despite viral immune evasion, the immune system effectively repels most HPV infections, and is associated with strong localized cell mediated immune responses. New prophylactic L1 virus-like protein vaccines for HPV 16 and 18 and HPV 6, 11, 16, and 18 are in phase 3 trials. Available data suggests that these vaccines are safe, produce high levels of antibodies, and are effective at preventing HPV infection.