An adenovirus type 5 (AdV5) vector encoding an envelope domain III-based tetravalent antigen elicits immune responses against all four dengue viruses in the presence of prior AdV5 immunity

Dengue is a mosquito-borne viral disease caused by four antigenically distinct serotypes of dengue viruses (DENVs). This disease, which is prevalent in over a hundred tropical and sub-tropical countries of the world, represents a significant global public health problem. A tetravalent dengue vaccine capable of protecting against all four DENV serotypes has been elusive so far. Current efforts are focused on producing a tetravalent vaccine by mixing four monovalent vaccine components. In this work, we have utilized a discrete carboxy-terminal region of the major DENV envelope (E) protein, known as domain III (EDIII), which mediates virus entry into target cells and contains multiple serotype-specific neutralizing epitopes, to create a chimeric tetravalent antigen. This antigen derived by in-frame fusion of the EDIII-encoding sequences of the four DENV serotypes was expressed using a replication-defective recombinant human adenovirus type 5 (rAdV5) vaccine vector. This rAdV5 vector induced cell-mediated immune responses and virus-neutralizing antibodies specific to each of the four DENVs in mice. Interestingly, anti-AdV5 antibodies did not suppress the induction of DENV-specific neutralizing antibodies. We observed that anti-AdV5 antibodies in the sera of immunized mice could promote uptake of a rAdV5-derived reporter vector into U937 cells, suggesting that pre-existing immunity to AdV5 may in fact facilitate the uptake of rAdV5 vectored vaccines into antigen presenting cells. This work presents an alternative approach to developing a single component tetravalent vaccine that bypasses the complexities inherent in the currently adopted four-in-one physical mixture approach.     

Novel IgE peptide-based vaccine prevents the increase of IgE and down-regulates elevated IgE in rodents

BACKGROUND: Immunotherapy with anti-IgE antibodies for treatment of allergy is promising but a short half-life and extremely high cost limit its application. OBJECTIVE: We sought to develop IgE vaccines that induce longer-lasting auto-antibodies to neutralize self-IgE as an alternative therapy. METHODS: The vaccine was made by conjugating three synthetic peptides corresponding to human IgE receptor-binding sites to a carrier, hepatitis B surface antigen. To test the immunogenicity of the vaccine, rats were immunized with the vaccine or hepatitis B surface antigen as control. Serum IgG titres to human IgE and the IgE of other species were measured. The inhibition by rat antisera of the binding of human IgE to its receptor was assessed by ELISA, flow cytometry analysis, and passive cutaneous anaphylaxis (PCA), and its ability to recognize receptor-bound IgE was examined. The in vivo effect of the vaccine was evaluated in trichosanthin-sensitized mice and rats. In the preventative study, vaccination started before sensitization commenced, while in the treatment study, vaccination started after sensitization. Sensitized mice and rats receiving injections of the carrier served as controls. Trichosanthin-specific IgE was measured using PCA. RESULTS: Sera from vaccine-immunized rats contained high titre antibodies that reacted with soluble and plate-bound but not with receptor-bound human IgE; they also reacted with mouse, rat, and dog IgE. Furthermore, the sera inhibited the binding of human IgE to its receptor in a dose-dependent manner. In preventative and treatment studies, serum trichosanthin-specific IgE levels were significantly reduced in vaccinated groups compared with controls. CONCLUSION: Antibodies against self-IgE can be induced by IgE peptide-based vaccines, which are effective in preventing the increase of IgE and in down-regulating IgE in sensitized animals.     

高危人群微量乙肝疫苗免疫效果动态观察

采用微量乙肝疫苗（总剂量为６μｇ）对ＨＢＶ高流行区居民进行随机对照研究，免疫Ⅰ组（疫苗＜８℃保存）Ｔ１２抗体阳转率和保护率分别为９０．８％和８７．０％，和对照组相比，差异显著（Ｐ均＜０．００１）；和常规剂量（总剂量９０μｇ）比，其抗体阳转率和保护率基本相同。提示ＨＢＶ高流行区可用微量乙肝苗代替常量乙肝苗进行预防接种。免疫Ⅰ组和免疫Ⅱ组（乙肝疫苗室温保藏２８℃±）免疫效果和保护率基本相同，认为室温条件下乙肝疫苗６个月内效价不变。     

重组酵母乙肝疫苗免疫效果研究

目的研究重组酵母乙肝疫苗对青少年学生的免疫效果。方法同时对３６５名乙肝病毒血清学指标（ＨＢＶ－Ｍ）不同感染状况的学生进行免疫监测。随机分为两组，Ａ组：１８３人，接种剂量１０－５－５（μｇ），Ｂ组：１８２人，接种剂量５－５－５（μｇ），用ＥＬＩＳＡ法，在全自动酶标分析仪上测定。结果１．重组酵母乙肝疫苗对青少年免疫效果良好，抗－ＨＢｓ阳性率达９７％以上；２．对ＨＢＶ－Ｍ不同感染状况的学生，免疫后均无不良反应。结论ＨＢＶ易感者和感染者接种疫苗后免疫效果均好。在青少年中普种乙肝疫苗可不筛查ＨＢＶ－Ｍ。     

Vaccination against the cat flea Ctenocephalides felis felis

Non-chemical control of haematophagous parasites is a desirable goal. We report here on the use of concealed antigens from the major digestive organ of the cat-flea as vaccine components. Rabbits were immunized with various antigens from cat flea midguts, and immunoglobulin from these rabbits was fed to cat fleas in an artifical feeding system. Antibody produced against soluble antigens from the midguts of fed fleas was able to kill fleas in this system. Dogs were then immunized with various antigen preparations, and challenged for a week with live fleas. Significantly fewer live fleas were recovered from dogs immunized with fed midgut supernatant, and recovered live female fleas produced significantly fewer eggs. This study indicates the possibility of vaccination as a means of control of flea, and possibly other blood sucking insect populations.     

冻干水痘减毒活疫苗最小免疫剂量的研究

通过临床研究确定冻干水痘减毒活疫苗的最小免疫剂量 ,为制定规程中的免疫剂量提供科学依据。观察对象接种不同免疫剂量的冻干水痘减毒活疫苗后 ,于接种前和接种后 6周采血 ,采用荧光抗膜抗体 (FAMA)法检测其抗体阳转率和几何平均滴度 (GMT)。接种不同免疫剂量的疫苗 ,抗体阳转率差异无显著的统计学意义。疫苗中抗原含量在 2 5 0 0 0PFU/ml和 2 0 0 0PFU/ml之间 ,GMT差异无显著的统计学意义 ,但 2 5 0 0 0PFU/ml、2 0 0 0PFU/ml与 2 0 0PFU/ml之间抗体GMT的差异有极显著的统计学意义。研究结果表明 ,2 0 0 0PFU/ml为冻干水痘减毒活疫苗的最小免疫剂量。     

水痘疫苗接种的成本效益

水痘是一种常见的急性、高传染性的疾病 ,可感染儿童、成人。 1974年日本首先研制成功Oka株水痘减毒活疫苗 ,1984年世界卫生组织批准水痘减毒活疫苗用于婴幼儿预防接种 ,许多国家陆续开展了水痘疫苗预防接种 ,不仅能取得良好的防病效果 ,而且可较大地减轻疾病负担。对儿童、青少年、成人、育龄期妇女和免疫功能抑制患者分别进行的经济学评价表明 ,接种水痘疫苗具有较好的成本效益结果。     

新生儿重组酵母乙肝疫苗接种免疫的研究

目的：探讨重组酵母乙肝疫苗新生儿接种后抗体应答持续时间，强化复种的必要性。方法：常规对新生儿0d(出生后当天)、1月、6月接种重组酵母乙肝疫苗后检测抗体应答情况，再随机分两组，一组为强化组，一组为常规组，并随访其5年的抗体应答情况。结果：新生儿常规接种法，于12个月后有一明显抗体应答下降期(0d、1月、6月、12月)，强化组乙肝表面抗体形成率高，持续时间均高于常规接种法。结论：新生儿乙肝疫苗0d、1月、6月、12月接种法有较好的远期保护效果，对现有的0d、1月、6月新生儿乙肝疫苗常规接种法，有强化接种的必要。     

Licensing and control authority batch release of influenza vaccine in Germany in accordance with EEC regulations

The epidemiological situation calls for almost yearly changes in the antigenic composition of influenza vaccine, thus necessitating fresh licensing procedures. Since the time for bringing a new vaccine onto the market should be relatively short, the following work of all parties involved must be done expeditiously: 1) WHO recommendations on new virus strains and their subsequent adaptation by the EEC (February/March); 2) Distribution of the new virus strains to the International Reference Centers for Influenza in the UK and USA (February/ March); the centers later issue reference materials for the determination of the haemagglutinin antigen concentration (April/May); 3) Production and testing of seed virus by manufacturers, as well as validation of the producer's inactivation process for the new virus strains (May/June); 4) Licensing of the vaccines by the National Control Authority (Paul-Ehrlich-Institute) (June/July); in the case of previously licensed products, the procedure is limited essentially to the approval of the detailed protocol of production and tests on the new virus strains, clinical studies not being required before licensing because of a lack of time; 5) Paul-Ehrlich-Institute's test for batch release, according to Directive 89/342/EEC, besides protocol approval, conducts material testing of the endotoxin and antigen content of each vaccine lot; the assay for the antigen quantification is especially laborious and sometimes must be repeated because of test invalidity.     

恶性疟P190抗原保守区Ⅰ、Ⅴ基因的亚克隆及在大肠杆菌中高效表达

作者采用PCR方法克隆了我国海南省FCC1/HN株P190抗原两个保守区基因,分别定名为P190CRI和P190CRV。基因片段经纯化后连接到pUC18载体中进行DNA序列分析,结果显示:除了P190CRV中有5个碱基变换外,其余序列均与MAD20型序列一致。经序列分析的两个基因片段分别与pGEX-2T载体连接,经双酶切鉴定后转化感受态JM109(DE_3)大肠杆菌进行高效融合表达,并且用Sepharose 4B-谷胱甘肽层析柱进行亲和纯化,结果为:两个插入基因片段均得到高效融合表达,经一步亲和纯化后就取得高纯度的重组蛋白。