衣原体疫苗的研究进展

衣原体是一类严格真核细胞内寄生、具有独特发育周期的原核细胞型微生物。其分布于世界各地,感染宿主广泛,引起人和动物多种疾病,临床表现复杂,需要寻找一种有效疫苗来加强免疫保护以预防衣原体感染。以亚单位疫苗及相关新策略为重点,就衣原体疫苗的研究状况作一简要介绍。     

衣原体质粒蛋白Pgp3的研究进展

衣原体中普遍含有一个7.5 kb左右的隐蔽性质粒,在衣原体物种中高度保守。Pgp3为该质粒编码的相对分子质量约28 000的免疫原性蛋白,能分泌到宿主细胞胞质中。在衣原体感染期间人类抗体可识别Pgp3的天然三聚体结构。Pgp3在衣原体致病机制中起重要作用,是诱导输卵管积液的主要毒力因子,能中和抗菌肽LL37的抗衣原体活性,且其DNA疫苗对衣原体感染具有一定的保护作用。本文就Pgp3的结构、在衣原体致病中的作用及其在疫苗与诊断抗原方面的应用进行简要概述,为进一步研究衣原体感染的发病机制及其诊断与预防提供新的思路。     

衣原体疫苗研究进展

衣原体是一类专一细胞内寄生的人兽共患病病原体,所引起的动物及人类疾病相当广泛。本文以亚单位疫苗及DNA疫苗为重点,对衣原体疫苗的研究状况做了简要的介绍。     

衣原体疫苗的研究动态

衣原体是一类原核细胞型微生物,也是一类重要的人兽共患病原体,所引起的动物及人类疾病相当广泛.人类和动物中的许多被感染者呈无症状携带状态,因此仅对有症状者进行治疗不能有效地控制疾病播散.疫苗接种无疑是一种较为经济,且能在更大程度上干扰衣原体流行的策略.本文简要回顾了衣原体疫苗的发展史,并对当今衣原体疫苗的研究进展、面临的问题进行了综合分析.     

抵抗女性生殖道沙眼衣原体感染的免疫新策略

沙眼衣原体是引起沙眼和泌尿生殖道感染的主要病原体。据世界卫生组织2015年统计,全球每年约有1.3亿沙眼衣原体感染新发病例。研究表明CD4^+Th1型细胞免疫应答在抵抗沙眼衣原体感染中发挥着重要作用。因此,研究者依照抗沙眼衣原体感染的免疫应答特点,构建出许多候选疫苗,但都没有成功地应用于临床。近年研究发现,生殖道黏膜组织不仅存在体液免疫和细胞免疫,还驻留着一些引人注目的免疫细胞,提示增强黏膜免疫可作为预防沙眼衣原体感染的潜在途径,是抵抗生殖道沙眼衣原体感染的免疫新策略。本文全面概述了黏膜免疫与女性生殖道沙眼衣原体感染的研究进展,并为今后研制沙眼衣原体疫苗提供一些建议。     

沙眼衣原体分型的研究进展

沙眼衣原体是发展中国家致盲的主要病因和发达国家性传播疾病的重要病原。沙眼衣原体分型研究,在血清学诊断,分子流行病学研究,疫苗的研制等方面均有重要意义,本文就沙眼衣原体分型技术的进展作了一概述。     

沙眼衣原体生殖道感染的小鼠模型及其应用

沙眼衣原体生殖道感染是严重危害人类生殖健康的一种常见的性传播疾病,研制安全、有效的疫苗是控制其感染的有效措施。在疫苗的研制中选择合适的动物模型非常重要。近几十年来学者们建立了多种沙眼衣原体生殖道感染的小鼠模型,根据接种途径可分为阴道内接种和子宫或卵巢囊内接种两大类。研究发现不同模型各有利弊,本文对两大类沙眼衣原体生殖道感染小鼠模型及其应用进行了综述。     

沙眼衣原体抗原成分的研究进展

沙眼衣原体的感染率不断增加,其危害也越来越大。在欧、美等国和地区,由沙眼衣原体所致性传播疾病已超过淋病奈瑟菌而居首位。当前对沙眼衣原体的研究较多,本文概述了近年来对沙眼衣原体抗原成分的研究进展及其在分型、诊断、致病性、疫苗研究方面的意义。     

Pgp3生物学特性与致病机制研究进展

衣原体具有广泛的致病谱，能够引起多种疾病，而分泌性蛋白在衣原体致病过程中发挥了重要的作用。Pgp3 (plasmid gene protein 3)是由衣原体质粒基因编码的一种主要定位于宿主细胞质的分泌性蛋白，具有调控炎症反应、细胞凋亡、自噬等多种生物学功能。Pgp3也是一种免疫优势抗原，可用于衣原体疾病的诊断和作为疫苗研制的靶点。全面、深入地研究该蛋白功能将有助于进一步了解衣原体的致病机制，为衣原体感染的诊断和防治提供新的思路。     

肺炎嗜衣原体热休克蛋白60的研究进展

肺炎嗜衣原体是严格的细胞内寄生菌,具有独特的发育周期,是重要的呼吸道疾病病原菌,与动脉硬化等慢性心血管疾病也有关系。在肺炎嗜衣原体感染中,热休克蛋白60(Cp-HSP60)是重要的致病因素,对树突状细胞、上皮细胞、平滑肌细胞、巨噬细胞的正常功能都有影响,能够促进T细胞向Th1型分化。经过基因序列分析及氨基酸序列比对,Cp-HSP60与其他衣原体HSP60具有很高的同源性。由于HSP60高度保守,Cp-HSP60与人的HSP60在慢性疾病病理过程中是否存在交叉反应仍存在争议。疫苗是控制传染的有效措施,应用重组Cp-HSP60和表达Cp-HSP60的DNA疫苗在小鼠实验中对肺炎嗜衣原体的感染有一定的保护作用,在肺部能产生免疫记忆。     

Vaccines for Chlamydia infections of the female genital tract.

Genital infection with Chlamydia trachomatis is an escalating global public health concern causing considerable morbidity and socioeconomic burden worldwide. Although antibiotics are used to treat symptomatic urogenital infections, chlamydial infection remains asymptomatic in approximately 50% of infected men and 70% of infected women. The major clinical manifestations of genital chlamydial infection in women include mucopurulent cervicitis, endometritis and pelvic inflammatory disease. Genital infection with C. trachomatis markedly enhances the risk for reproductive tract sequelae in women, including tubal factor infertility, chronic pain and ectopic pregnancy. Definitive infection control of chlamydial infections will likely be achievable through a safe and efficacious vaccine. This will require identifying protective chlamydial antigens in animal models as well as identifying effective adjuvants and delivery systems that target subunit vaccines to immune inductive sites or secondary lymphoid tissues, and will be safe for use in humans.     

A Vibrio cholerae ghost-based subunit vaccine induces cross-protective chlamydial immunity that is enhanced by CTA2B, the nontoxic derivative of cholera toxin

The Vibrio cholerae ghost (rVCG) platform is an effective carrier and delivery system for designing efficacious Chlamydia vaccines. We investigated whether CTA2B, the nontoxic derivative of cholera toxin, can augment protective immunity conferred by an rVCG-based chlamydial vaccine and enhance cross-protection against heterologous chlamydial strains. An rVCG vaccine coexpressing chlamydial major outer membrane protein and CTA2B was genetically constructed and antigens were targeted to the inner membrane of V. cholerae before ghost production by gene E -mediated lysis. Effective immunomodulation by CTA2B was demonstrated by the ability of the vaccine construct to enhance the activation and maturation of dendritic cells in vitro . Also, C57BL/6 mice immunized via mucosal and systemic routes showed increased specific mucosal and systemic antibody and T-helper type-1 (Th1) responses, irrespective of the route. The enhanced production of IFN-γ, but not IL-4 by genital mucosal and splenic T cells, indicated a predominantly Th1 response. Clearance of the Chlamydia muridarum vaginal infection was significantly enhanced by codelivery of the vaccine with CTA2B, with the intravaginal route showing a moderate advantage. These results indicate that the rVCG-based vaccine is capable of inducing cross-protection against heterologous chlamydial serovars and that incorporation of mucosal adjuvants, such as CTA2B in the rVCG delivery platform, may enhance protective immunity.     

The requirement for potent adjuvants to enhance the immunogenicity and protective efficacy of protein vaccines can be overcome by prior immunization with a recombinant adenovirus

A central goal in vaccinology is the induction of high and sustained Ab responses. Protein-in-adjuvant formulations are commonly used to achieve such responses. However, their clinical development can be limited by the reactogenicity of some of the most potent preclinical adjuvants and the cost and complexity of licensing new adjuvants for human use. Also, few adjuvants induce strong cellular immunity, which is important for protection against many diseases, such as malaria. We compared classical adjuvants such as aluminum hydroxide to new preclinical adjuvants and adjuvants in clinical development, such as Abisco 100, CoVaccine HT, Montanide ISA720, and stable emulsion-glucopyranosyl lipid A, for their ability to induce high and sustained Ab responses and T cell responses. These adjuvants induced a broad range of Ab responses when used in a three-shot protein-in-adjuvant regimen using the model Ag OVA and leading blood-stage malaria vaccine candidate Ags. Surprisingly, this range of Ab immunogenicity was greatly reduced when a protein-in-adjuvant vaccine was used to boost Ab responses primed by a human adenovirus serotype 5 vaccine recombinant for the same Ag. This human adenovirus serotype 5-protein regimen also induced a more cytophilic Ab response and demonstrated improved efficacy of merozoite surface protein-1 protein vaccines against a Plasmodium yoelii blood-stage challenge. This indicates that the differential immunogenicity of protein vaccine adjuvants may be largely overcome by prior immunization with recombinant adenovirus, especially for adjuvants that are traditionally considered poorly immunogenic in the context of subunit vaccination and may circumvent the need for more potent chemical adjuvants.     

Immunization trials with an avian chlamydial MOMP gene recombinant adenovirus

Chicks were inoculated with a live vector vaccine of avian chlamydial MOMP gene recombinant adenovirus to evaluate efficacy, safety and viability of the vaccine. Five batches of the recombinant adenovirus vaccines, which were prepared using the 22nd generation avian chlamydial MOMP gene recombinant adenovirus cultured in HEK293 cells, were used to vaccinate 7 days-old chicks negative for chlamydial antibody. The recombinant adenovirus vaccine was shown to be both safe and effective in inducing specific immunity in vaccinated chicks.     

Lipid and carbohydrate based adjuvant/carriers in immunology.

This review discusses various issues regarding vaccines; what are they and how they work, safety aspects, the role of adjuvants and carriers in vaccination, synthetic peptides as immunogens, and new technologies for vaccine development and delivery including the identification of novel adjuvants for mucosal vaccine delivery. There has been a recent increase of interest in the use of lipids and carbohydrates as adjuvants, and so a particular emphasis is placed on adjuvants derived from lipids or carbohydrates, or from both.     

The choice of adjuvants in Mycoplasma vaccines

The use of adjuvants in vaccine production is an important aspect of potent vaccines. This investigation was concerned with finding the most efficient adjuvants for use in Mycoplasma vaccines produced in Nigeria. Four different vaccines were produced from the Gladysdale strain of Mycoplasma mycoides subspecies mycoides. They differed depending on the type of adjuvants used. Each vaccine was used to vaccinate eight cattle using a dose of 1 ml. Two other groups of eight cattle were used as controls. One of the two groups received 1 ml dose of inactivated Gladysdale vaccine without adjuvant while the second group received 1 ml dose of saline. The number of cattle that had the peak complement fixing (CF) antibody titres of 1/80 in each group of cattle was four for vaccine containing aluminium hydroxide gel, eight for vaccine containing liquid paraffin, one for vaccine containing sodium alginate and one for vaccine without adjuvant. Seven cattle from the group vaccinated with vaccine containing Freund's incomplete adjuvant had peak CF antibody titres of 1/80 or higher. The two groups vaccinated with vaccine containing liquid paraffin and Freund's incomplete adjuvant survived challenge at 6 months post vaccination. Freund's incomplete adjuvant and liquid paraffin containing 10% Arlacel A are the most efficient adjuvants.     

粘膜免疫佐剂研究进展

粘膜免疫佐剂在新型疫苗的设计中具有重要作用。常用的粘膜免疫佐剂主要包括细菌性物质、细胞因子以及抗原递送系统。本文综述了这些佐剂的研究进展,以期为新型疫苗研究提供参考。     

Endocine?, N3OA and N3OASq; Three Mucosal Adjuvants That Enhance the Immune Response to Nasal Influenza Vaccination

Annual outbreaks of seasonal influenza are controlled or prevented through vaccination in many countries. The seasonal vaccines used are either inactivated, currently administered parenterally, or live-attenuated given intranasally. In this study three mucosal adjuvants were examined for the influence on the humoral (mucosal and systemic) and cellular influenza A-specific immune responses induced by a nasally administered vaccine. We investigated in detail how the anionic Endocine™ and the cationic adjuvants N3OA and N3OASq mixed with a split inactivated influenza vaccine induced influenza A-specific immune responses as compared to the vaccine alone after intranasal immunization. The study showed that nasal administration of a split virus vaccine together with Endocine™ or N3OA induced significantly higher humoral and cell-mediated immune responses than the non-adjuvanted vaccine. N3OASq only significantly increased the cell-mediated immune response. Furthermore, nasal administration of the influenza vaccine in combination with any of the adjuvants; Endocine™, N3OA or N3OASq, significantly enhanced the mucosal immunity against influenza HA protein. Thus the addition of these mucosal adjuvants leads to enhanced immunity in the most relevant tissues, the upper respiratory tract and the systemic circulation. Nasal influenza vaccination with an inactivated split vaccine can therefore provide an important mucosal immune response, which is often low or absent after traditional parenteral vaccination.     

Influence of adjuvants in inducing immune responses to different epitopes included in a multiepitope,multivalent, multistage Plasmodium falciparum candidate vaccine (FALVAC-1) in outbred mice

FALVAC-1, a vaccine against Plasmodium falciparum was developed by joining 21 epitopes from P. falciparum vaccine antigens and an universal T helper epitope from tetanus toxoid. Since adjuvants influence different aspects of immune responses, in this study we investigated the effect of four adjuvants aluminum hydroxide (alum), nonionic copolymer adjuvant P1005 (water-in-oil emulsion), CpG oligodeoxynucleotides (ODN), and QS-21 in eliciting immune responses in outbred mice. QS-21 and copolymer adjuvants were the best formulations in inducing higher and long-lasting antibody titers to the whole vaccine compared to alum and CpG. QS-21 was the only adjuvant to elicit predominantly IgG2a response and antibodies reactive with all epitopes incorporated in the vaccine construct. Vaccine elicited antibodies recognized sporozoites and asexual blood-stage parasites. FALVAC-1 immunized mice induced lymphoproliferative and IFN-gamma response to the vaccine. QS-21 and CpG adjuvants were able to elicit T proliferative responses to 20 of the 22 epitopes in the vaccine. In conclusion, this study demonstrated that with suitable adjuvant such as QS-21, it is possible to elicit immune responses to most of the epitopes included in the FALVAC-1 vaccine.     

不同佐剂肾综合征出血热纯化疫苗体液免疫效果的研究

在肾综合征出血热(HFRS)纯化疫苗原液中分别加入Al(OH)3、IL-2、GM-CSF、CFA等佐剂的一种或两种,以不加佐剂的纯化疫苗原液作为对照,分别免疫BALB/c小鼠,定期进行眼眶采血,用ELISA法检测血清中抗HFRS病毒的抗体水平。用不同佐剂的HFRS纯化疫苗免疫BALB/c小鼠后,其抗体产生的时间和滴度均不同。佐剂组与对照组相比抗体产生早且(或)滴度高,IL-2佐剂组在免后第3天就可以检测到抗体;联合使用两种佐剂组与单独使用一种佐剂组相比,抗体产生早、滴度高。结果表明,上述各种佐剂对HFRS纯化疫苗诱导BALB/c小鼠产生的免疫应答均有一定的增强作用;IL-2对早期免疫应答、早期抗体的产生有显著意义;联合应用两种佐剂疫苗的免疫效果优于只加其中一种佐剂的疫苗。