Immunogenicity of a monovalent pandemic influenza A H1N1 vaccine in health-care workers of a university hospital in Japan

A phase III observational study evaluating a single-dose of an inactivated, split-virus, unadjuvanted AH1pdm vaccine in HCW was conducted. A safe and effective vaccine was needed after the emergence of AH1pdm in April 2009. We analyzed the immunogenicity and safety of the vaccine. A total of 409 subjects were enrolled and given 15 μg hemagglutinin antigen by s.c. injection. Antibody titers were measured using hemagglutination-inhibition antibody assays before vaccination and 28 days after. The co-primary immunogenicity end-points were the proportion of subjects with antibody titers of 1:40 or more, the proportion of subjects with either seroconversion or a significant increase in antibody titer, and the factor increase in geometric mean titer. We collected 389 pair samples. Antibody titers of 1:40 or more were observed in 148 of 389 subjects (38.0%, 95% CI: 33.2-42.9). The immunogenicity was also confirmed in other end-points, but was not sufficient and was lower than in previous reports. A total of 96 of adverse events was reported: 51 local events and 57 systemic events. There were 12 subjects with both local and systemic events. Nearly all events were mild to moderate except in four subjects. A single 15-μg dose of AH1pdm vaccine did not induce sufficient immunogenicity in HCW, with mild-to-moderate vaccine-associated adverse events. We need to consider further improvement of the AH1pdm vaccine program in HCW for the prevention of nosocomial infection, as well as for the benefit of HCW.     

寨卡病毒引发小头症?关系越确定,防治越迫切!

自2015年初至今,寨卡病毒(Zika virus,ZIKV)以巴西为首先后在数十个国家和地区暴发流行。几乎同时,与日俱增的小头症患儿使全球对此陷入警惕状态。目前,全球正在积极探索ZIKV感染所引发的各种神经系统疾病。在越来越多证据表明在细胞水平和动物模型中ZIKV能直接损伤胚胎脑部发育的同时,ZIKV感染者的防治需求也越来越迫切。本文从ZIKV的流行病学、与小头畸形因果关系的研究进展及其预防疫苗和治疗药物的研究现状等方面进行概述。     

表达T~+Pm保护性抗原的重组猪霍乱沙门氏菌C500株的构建及其生物学特性

【目的】本研究利用Asd+平衡致死系统构建表达巴氏杆菌毒素(Pasteurella multocida toxin,PMT)的重组猪霍乱沙门氏菌株,并对重组菌株的生物学特性进行比较研究。【方法和结果】通过基因克隆的方法构建表达PMT的重组质粒pYA-PmtC,再将其电转化减毒猪霍乱沙门氏菌C500的asd基因缺失株C501,构建口服活疫苗菌株C501(pYA-PmtC)。研究结果表明重组菌株C501(pYA-PmtC)的生化特性、血清型和生长速度与亲本菌株C500一致;在没有选择压力的条件下,C501(pYA-PmtC)能够稳定遗传重组质粒及其外源基因片段,并能稳定、高效、分泌性表达30.5kDa的外源保护性抗原rPmtC。C501(pYA-PmtC)腹腔感染BALB/c小鼠的LD50为8.5×106CFU,毒力稍低于C500(LD50为4.4×106CFU);口服接种C501(pYA-PmtC)和C500的所有仔猪未见任何发病症状,两者没有显著差别。【结论】本研究利用Asd+平衡致死系统的原理构建表达T+Pm保护性抗原重组猪霍乱沙门氏菌弱毒菌株C501(pYA-PmtC),为进一步开发猪萎缩性鼻炎-副伤寒的双价基因工程疫苗奠定基础。     

Oral and intranasal administration of somatostatin DNA vaccine mediated by attenuated Salmonella enterica serovar Typhimurium to promote growth of piglets

An attenuated strain of Salmonella typhimurium has been used as a carrier for oral and intranasal genetic immunization. Here, we evaluate the efficacy of a vaccine strain of S. typhimurium. CSO22 (pGM-CSF/SS, plasmid granulocyte-macrophage colony-stimulating factor/somatostatin) expressing two copies of SS genes. A total of 115 piglets, aged 2 months old, were either orally or intranasally immunized against the vaccine strain CSO22 (pGM-CSF/SS) with three dosages (5 × 10(10) colony forming units (CFU), 5 × 10(9) CFU and 5 × 10(8) CFU). For oral immunization, the specific anti-SS antibodies were detected in the immunized piglets. The levels of SS antibodies in the high-dose immunized group (5 × 10(10) CFU) were significantly higher than that in the phosphate buffered saline immunized group (P < 0.01) and 40% of animals were positive in SS antibodies in the high-dose immunized group. Moreover, the weight gain of the high-dose group was increased by 20.86%, 10.26% and 15.30% during 4, 8 and 12 weeks, respectively, after immunization in comparison to the control. For intranasal immunization, the growth of the low-dose group was increased by 10.23% in the whole test period (12 weeks). In conclusion, our results suggest that the recombinant strain could elicit anti-SS antibodies and improve the growth performance of immunized piglets, and that the oral immunization program is better than the intranasal program.     

EV71灭活疫苗（人二倍体细胞）在恒河猴婴猴模型中的免疫保护性分析

肠道病毒71型作为引起儿童群体常见传染性手足口病（HFMD）的主要病原,具有导致少量感染个体出现脑炎等神经系统病变以及相关心肺功能衰竭的病理学特性．因此其预防性疫苗的研发具有重要的公共卫生意义．在前期工作的基础上,一种EV71灭活病毒疫苗（人二倍体细胞）在本研究中基于恒河猴婴猴模型进行了相应的免疫保护性分析．以160EU剂量对2～3月龄婴猴进行0,4周免疫后,动物在第4周接受了剂量为10。～CCID50的病毒经呼吸道的攻击．对病毒攻击后动物在14天内的临床症状、血液生物学、器官病原学分布以及病理学检测的动态观察表明,经疫苗免疫的动物未出现对照动物所具有的特征性临床表现,其血液生物学及病理学检测均无异常．同时,器官病原学分布亦呈阴性．结合动物中和抗体的明确增长及对照动物的综合表现分析,本文的工作证实了该EV71灭活病毒疫苗（人二倍体细胞）在恒河猴婴猴体内的免疫保护性．     

Immunological dynamics in response to two anthrax vaccines in mice

In order to understand the variation of humoral and cellular immune responses to A16R live spore and AVA vaccine and to identify efficient immunological parameters for the early evaluation of post immu- nization in mice, we dynamically monitored the antibody production and cellular responses after the vaccination of Balb/C mice with the anthrax vaccines. The results show that both anti-AVA and anti-Spore antibodies were detectable in the A16R live spore vaccinated group while high titers of anti-AVA antibodies but not anti-Spore antibodies existed in the AVA-immunized group. IgG1 and IgG2 were the major subtypes of IgG in both of the two groups. However, the IgG2a level was significantly higher in the A16R group than in the AVA group. At the cellular level, responses of antigen-specific TH2, TH1 and plasma cells were detected. The peripheral TH2 responses could be seen on day 5 after vac- cination, and remained at a high level throughout the experiment (from day 5 post primary immuniza- tion to day 60 post the tertiary immunization); the TH1 responses to A16R vaccine appeared on day 5, while the responses to AVA could only be detected by day 7 after the secondary immunization; a low level of TH1 responses could be observed at the end of the experiment. Antigen-specific plasma cells could be found in the peripheral blood of both the immunized groups, however, the responses in the A16R group appeared earlier, lasted longer, and shown an ascending tendency until the end of the ex- periment when the plasma cell responses in the AVA group were reduced to a very low level. The re- sults suggest that the multiple antigen containing A16R live spore vaccine induces better immune re- sponses than AVA. Combined with serum antibody titers, TH2, TH1 and plasma cell responses could be used as immunological parameters for the evaluation of vaccine efficacy. These findings may afford new insight into the early evaluation of vaccination as well as being a powerful strategy for vaccine development.     

家养犬、猫及野生动物中狂犬病病毒流行病学调查及我国不同类型狂犬病疫苗免疫效果观测研究

选择我国狂犬病高发地区(湖南、贵州)、低发地区(江苏、武汉)和无狂犬病报告地区(沈阳)等三种不同类型的地区,开展针对家养犬、猫和啮齿类动物,以及蝙蝠等野生动物的狂犬病病毒带毒率的流行病学调查,对分离到的病毒株在抗原型别、基因变异以及与现行疫苗是否匹配等方面进行分析、比较研究。结果显示:我国狂犬病的主要宿主动物为犬,捕获犬总带毒率为2.56%;犬中狂犬病病毒的监测点最高阳性检出率达到20.0%;啮齿类动物及蝙蝠等野生动物在本次研究未检测到狂犬病病毒。我国自主研制成功的以aG株和CTN株为毒种的现行人用狂犬病疫苗,经应用研究发现,CTN株的糖蛋白基因与本研究分离到的街毒核酸序列更接近。为进一步评价现行疫苗的有效性,在5个观察点分别以aG株和CTN株毒种生产的疫苗接种两组人群(每组各约50人),结果显示均未出现中、强度反应,疫苗免疫后第7d和14d产生的中和抗体分别达到0.49IU/mL~0.52IU/mL和6.7IU/mL~7.53IU/mL;抗体阳转率分别为45.1%~47.9%和100%,表明这些疫苗具有良好的安全性和保护效果。     

流行性乙型脑炎活疫苗细胞免疫检测方法的探索

本文建立了流行性乙型脑炎活疫苗细胞免疫检测方法。采用纯系Ｂａｌｂ／ｃ（Ｈ－２ｄ）小鼠制备效应细胞,以同一品系Ｂａｌｂ／ｃ（Ｈ－２ｄ）小鼠原代肾细胞为靶细胞。当效靶细胞比例为２０∶１,杀伤时间为４小时,ＭＴＴ反应时间为４小时,细胞毒性Ｔ淋巴细胞（ＣＴＬ）杀伤作用最强。利用该法对乙脑活苗和死苗免疫小鼠进行了ＣＴＬ活性测定,结果表明该法重复性好,活苗诱导ＣＴＬ杀伤作用强于死苗     

HPV16型E7复制型DNA疫苗诱发的抗肿瘤免疫反应

为了研制有效的疫苗 ,用于HPV16型重度感染和与其感染相关的宫颈癌晚期病人手术后的免疫治疗 ,用复制型DAN疫苗载体 pSCA1,在其CMVIE启动子之下插入修饰的HPV16型E7基因mE7- 3( 2 4G、2 6G、6 7R) ,构建成 pSCA1mE7- 3复制型DNA疫苗。以重组质粒免疫C5 7BL/ 6小鼠 ,检测诱发的特异性CTL活性 ;将免疫后的小鼠用TC - 1肿瘤细胞攻击 ,观察免疫保护效果。实验结果显示 :pSCA1mE7- 3复制型DNA疫苗能诱导小鼠产生针对TC - 1肿瘤细胞的特异性CTL反应 ;复制型DNA疫苗免疫后的小鼠能耐受 1× 10 4 TC - 1细胞的攻击 ,成瘤时间推迟 ,并且成瘤率明显下降 ,部分小鼠得到保护能免受肿瘤攻击。因此pSCA1mE7- 3复制型DNA疫苗可作为HPV16相关肿瘤的癌前病变及中晚期病人术后免疫治疗的候选疫苗。     

抗肿瘤多肽的研究新进展

抗肿瘤多肽具有分子质量小、特异性高、免疫原性低、生物利用度高等优点,且易于合成和改造,其在肿瘤治疗领域的应用研究近 年来受到广泛关注。目前,已有多种抗肿瘤多肽及其衍生物上市或进入临床研究,对于肿瘤的临床治疗具有重要价值。综述抗肿瘤多肽在 诱导肿瘤细胞凋亡、抑制肿瘤新生血管生成、抑制肿瘤细胞生长和转移以及用作疫苗和药物载体等方面的研究新进展。