Pandemic influenza vaccines - the challenges

Recent years' enzootic spread of highly pathogenic H5N1 virus among poultry and the many lethal zoonoses in its wake has stimulated basic and applied pandemic vaccine research. The quest for an efficacious, affordable and timely accessible pandemic vaccine has been high on the agenda. When a variant H1N1 strain of swine origin emerged as a pandemic virus, it surprised many, as this subtype is well-known to man as a seasonal virus. This review will cover some difficult vaccine questions, such as the immunological challenges, the new production platforms, and the limited supply and global equity issues.     

An adjuvanted pandemic influenza H1N1 vaccine provides early and long term protection in health care workers

Mass vaccination was the most effective prophylaxis for protecting the population during the influenza H1N1 pandemic. We have evaluated the tolerability, immunogenicity and kinetics of the antibody response to a monovalent oil-in-water (AS03) adjuvanted human pandemic split influenza A/California/7/2009 H1N1 (3.75 μg haemagglutinin) vaccine in health care workers. Vaccination elicited a rapid and early protective level of haemagglutination inhibition antibody from 6 to 7 days post vaccination, and by 14 to 21 days post vaccination, up to 98% of vaccinees had protective antibody titres which persisted for at least 3 months in 84-92% of subjects. A rapid induction of protective antibody is important in reducing community spread of pandemic influenza and in helping maintain the integrity of the health care system during the pandemic.     

Immune responses against SARS-coronavirus nucleocapsid protein induced by DNA vaccine

The nucleocapsid （N） protein of SARS-coronavirus （SARS CoV） is the key protein for the formation of the helical nucleocapsid during virion assembly. This protein is believed to be more conserved than other proteins of the virus, such as spike and membraneglycoprotein, In this study, the N protein of SARS-CoV was expressed in Escherichia coli DH5alpha and identified with pooled sera from patients in the convalescence phase of SARS.     

Small interfering RNA inhibits SARS-CoV nucleocapsid gene expression in cultured cells and mouse muscles

SARS-CoV is a newly identified coronavirus that causes severe acute respiratory syndrome （SARS）. Currently, there is no effective method available for prophylaxis and treatment of SARS-CoV infections. In the present study, the influence of small interfering RNA （siRNA） on SARS-CoV nucleocapsid （N） protein expression was detected in cultured cells and mouse muscles. Four siRNA expression cassettes driven by mouse U6 promoter targeting SARS-CoV N gene were prepared, and their inhibitory effects on expression of N and enhanced green fluorescence protein （EGFP） fusion protein were observed. A candidate siRNA was proved to down-regulate N and EGFP expression actively in a sequence-specific manner. The expression vector of this siRNA was constructed and confirmed to reduce N and EGFP expression efficiently in both cultured cells and adult mouse muscles. Our findings suggest that the siRNA should provide the basis for prophylaxis and therapy of SARS-CoV infection in human.     

基因载体、基因选择、基因转移与类风湿关节炎

目的:综合分析类风湿关节炎的基因治疗现状及应用前景。资料来源:应用计算机检索Pubmed及highwire1997-01/2006-06有关类风湿关节炎基因治疗的文献,检索词“gene therapy,rheumatoid arthritis,interleukin-1 receptor antagonist,soluble tumor necrosis factoreceptor”,并限定文章语言种类为English。资料选择:对检索到的类风湿关节炎基因治疗方面的相关信息进行整理,选取针对性强的文章。同一领域的文献则选择近期发表或权威杂志的文章。资料提炼:共检索到67篇相关文献,其中30篇文章符合要求。排除37篇,其中21篇系重复同一研究,16篇为Meta分析。资料综合:类风湿关节炎的基因疗法作为生物治疗的一种新趋势,在很短时间内从理论和实验室取得成功,为临床类风湿关节炎的治疗提供了新的思路。文章主要针对类风湿关节炎基因治疗的目的基因、转移载体、转移途径选择、基因表达调控以及临床应用前景等进行分析。结论:类风湿关节炎的基因治疗已在动物实验中取得了可喜的成就,许多研究已经证明其临床应用的价值,但临床应用安全性及有效性尚有待进一步观察。     

IgA肾病的治疗进展

IgA 肾病是最常见的原发性肾小球疾病,由于其发病机制尚未明确,目前仍无特异性治疗药物.临床上的治疗目标是有效降低蛋白尿,控制血压和(或) 高尿酸并减少肾组织进一步损伤,维持肾功能稳定.对反复发作的镜下血尿患者,扁桃体切除术作为治疗的一种手段;对单纯性血尿和病理改变较轻者,主要加强随访观察;对于有尿蛋白和(或)高血压的缓慢进展的IgA肾病,血管紧张素转化酶抑制剂和血管紧张素受体拮抗剂可用于大部分病例,必要时可使用糖皮质激素,也可应用细胞毒性药物或吗替麦考酚酯等免疫抑制剂进行治疗;病情进展较快的高危患者,可用糖皮质激素冲击治疗,或使用细胞毒药物或免疫抑制剂等强化治疗.     

注射用双黄连粉针剂与氨苄青霉素钠配伍血药浓度探讨

目的;研究氨苄青霉素与双黄连粉针剂配伍增强疗效的作用,方法：采用紫外分光光度法测定氨苄青霉素与双黄连配伍后,氨苄青霉素的血药浓度及单用氨苄青霉素的血药浓度。结果：比较配伍组与单用氨苄青霉组组的血药浓度,结果表明,前者在用２ｈ后,血中氨苄青霉素的浓度明显高于后者,结论：双黄连与氨苄青霉素配伍,可竞争性抑制氨苄青霉从肾小管分泌,从而提高氨苄青霉素的血药浓度,达可能是增强疗效的重要原因之一。     

美通宁片中褪黑素的含量测定

目的：制定美通宁片中褪黑素质量控制指标。方法：采用薄层扫描法测定美通宁片中褪黑素的含量。以苯;氯仿：甲醇（4：9：1）为展开剂。结果;通过方法学考察,平均回收率98．5％。变异系数RSD＝4．12％。结论：方法可靠、准确,操作简便可行。     

A phase I clinical trial of a PER.C6 cell grown influenza H7 virus vaccine

Avian influenza H7 viruses have transmitted from poultry to man causing human illness and fatality, highlighting the need for pandemic preparedness against this subtype. We have developed and tested the first cell-based human vaccine against H7 avian influenza virus in a phase I clinical trial. Sixty healthy volunteers were intramuscularly vaccinated with two doses of split H7N1 virus vaccine containing 12 μg or 24 μg haemagglutinin alone or with aluminium hydroxide adjuvant (300 μg or 600 μg, respectively). The vaccine was well tolerated in all subjects and no serious adverse events occurred. The vaccine elicited low haemagglutination inhibition and microneutralisation titres, although the addition of aluminium adjuvant augmented the antibody response. We found a higher number of antibody secreting cells and an association with IL-2 production in subjects with antibody response. In conclusion, our study shows that producing effective H7 pandemic vaccines is as challenging as has been observed for H5 vaccines.