Development and approval of live attenuated influenza vaccines based on Russian master donor viruses: Process challenges and success stories

Influenza is a viral infection that affects much of the global population each year. Vaccination remains the most effective tool for preventing the disease. Live attenuated influenza vaccine (LAIV) has been used since the 1950s to protect humans against seasonal influenza. LAIVs developed by the Institute of Experimental Medicine (IEM), Saint Petersburg, Russia, have been successfully used in Russia since 1987.In 2006, the World Health Organization (WHO) announced a Global action plan for influenza vaccines (GAP). WHO, recognizing potential advantages of LAIV over the inactivated influenza vaccine in a pandemic situation, included LAIV in the GAP.BioDiem Ltd., a vaccine development company based in Melbourne, Australia which held the rights for the Russian LAIV, licensed this technology to WHO in 2009. WHO was permitted to grant sub-licenses to vaccine manufacturers in newly industrialized and developing countries to use the Russian LAIV for the development, manufacture, use and sale of pandemic and seasonal LAIVs. To date, WHO has granted sub-licenses to vaccine manufacturers in China (Changchun BCHT Biotechnology Co., Ltd.), India (Serum Institute of India Pvt. Ltd.) and Thailand (Government Pharmaceutical Organization). In parallel, in 2009, IEM signed an agreement with WHO, under which IEM committed to supply pandemic and seasonal candidate vaccine viruses to the sub-licensees.This paper describes the progress made by collaborators from China, India, Russia and Thailand in developing preventive measures, including LAIV against pandemic influenza.     

Indoor radon measurement with The Lucas cell technique

Rn-222 is the most important source of natural radiation and is responsible for approximately half of the received dose from all sources. Most of this dose is from inhalation of the Rn-222 progeny, especially in closed atmospheres. A Lucas cell technique, using a portable device, “PRASSI” (SILENA mod. 5S), for Rn-222 measurements inside the Centre for Radiation Protection and Radioecology (ZSR), Hannover University was used. The portable radon monitor PRASSI is suitable for radon gas continuous or grab sampling measurements with the scintillation cell technique. In recognition of the wide periodic variations in concentration, measurements were made daily for extended periods. At the same time, meteorological variables, such as temperature and humidity were observed so that their influence on radon levels could be evaluated. The radon average concentration during the year was about 55.9 Bq/m³ which gives rise to an annual effective dose 2.2 mSv y⁻¹. The radon concentration is within the limits prescribed by the International Commission for Radiation Protection. A detailed analysis of radon distribution with seasonal variation is presented.     

6186例脑卒中患者发病时间的季节性分析

目的探讨青岛市区脑出血(CH)、脑梗死(CI)、蛛网膜下腔出血(SAH)发病时间的季节规律。方法收集青岛市1998年～2002年脑卒中患者6186例,其中CH1179人,CI4821人,SAH186人。圆分布分析探讨脑卒中患者发病时间的季节规律。结果CH冬季高发,平均角在1月份(P<0.05),男性患者的平均角在2月份(P<0.05),女性患者的平均角在1月份(P<0.05);CI秋季高发,男、女间无差别,平均角在10月份(P<0.05);SAH秋季高发,平均角在10月份(P<0.05),男性患者的平均角在9月份(P<0.05),女性患者的平均角在10月份(P<0.05)。结论青岛市的脑卒中发病具有季节性,在脑卒中预防工作中要充分考虑其发病的季节特点,并采取相应的措施。     

圆形分布法在蝇类季节消长规律中的应用

目的确定蝇类季节消长的高峰日和高峰时段,为制定蝇类防制措施提供科学依据。方法用圆形分布法统计分析绍兴市区2003-2004年蝇类密度监测数据。结果绍兴市区2003-2004年蝇类平均密度高峰日为8月4日,高峰时段为6月8日至9月30日。其中2003年蝇类密度高峰日为8月11日,高峰时段为6月17日至10月5日;2004年蝇类密度高峰日为7月29日,高峰时段为6月1日至9月26日。结论绍兴市区2年中蝇类消长有明显的季节性规律。     

Twice daily 4% Sodium Cromoglycate vs. 2% Sodium Cromoglycate used four times daily in seasonal (grass pollen) allergic conjunctivitis

It is well established that 2% Sodium Cromoglycate is an effective treatment for a number of allergic eye diseases. It has been shown to be non-toxic. It can be used longterm and in serious allergic problems it is a useful adjunctive therapy to steroids. The main problem with Sodium Cromoglycate is that the recommended dosage is a four times daily application and patient non-compliance is common. One of the main objectives of any therapy is to reduce the frequency of dosage and the current study has been designed to investigate the efficacy of a 4% solution of Sodium Cromoglycate, used twice daily, versus a 2% solution used four times daily in seasonal allergic conjunctivitis. A multicentre study, therefore, was carried out to assess the efficacy of both drugs and to assess any possibility of side effects. In addition, a unit dose was used, thus eliminating preservatives and it was used specifically in seasonal allergic conjunctivitis in the pollen season. This study showed that 4% Sodium Cromoglycate used twice daily was at least as affective as 2% Sodium Cromoglycate used four times daily.     

典型办公室内氡浓度水平的时间性变化

目的了解典型办公场所内氡浓度水平随时间变化规律,为开展办公室内氡浓度水平调查或评价提供有效方案。方法选取典型办公室1间,用脉冲电离室测氡仪AlphaGUARD～开展9个月的连续测量,通过对测量数据的统计,分析办公室内氡浓度水平的变化规律。结果在9个月内,办公室内氡浓度的最大日均值、周均值、月均值以及季度均值与相应的最小值比分别为6.27、2.63、1.41和1.09;周末与工作日平均氡浓度的比值为1.17,工作日中上、下班时间段的平均氡浓度比值为0.86。结论办公场所内氡浓度水平虽然随时间变化,但3个月的连续测量均值基本可反映办公室内氡浓度的年度均值。     

Factors affecting serotonin uptake into human platelets

Because of complexities in platelet serotonin uptake dynamics, we studied the influence of the time of day and year as well as the subject's age on uptake parameters. While the assay itself was quite reproducible, and the kinetic parameters of 5 HT uptake were stable over a few days, at a given time, within an individual, the variance was quite large when samples from different times of the day or year or from different individuals were compared. An inverse relationship between V _max (moles/cell number/time) and platelet number was found in data from a group of individuals, suggesting regulation of V _max not at the level of uptake capacity per cell, but in a manner that somehow takes into consideration the number of platelets in the subject's plasma. Indeed, expressing V _max in a new way (called total V _max), not based on V _max per cell or per 10⁷ cells but for the total number of platelets in the volume of PRP used, greatly reduced the scatter in the between-individuals and across-time data. While V _max (moles/cell number/time) exhibited only a trend toward reduction with age, for example, the decline in total V _max with subject age was statistically significant. It is suggested that total V _max (moles/time) may be a more physiologically relevant expression for an uptake function than V _max (moles/time/cell number).     

Androgenic control of porphyrin in the harderian glands of the male syrian hamster is modulated by the photoperiod,which suggests that the sexual differences in porphyrin concentrations in this gland are important functionally

Background: The porphyrin concentrations of the Harderian glands of Syrian hamsters show marked sexual differences, with male levels being much lower than those of females. Porphyrinogenesis is inhibited by androgens, so orchidectomy leads to elevated male porphyrin concentrations; however, a number of other procedures (some of which also lower androgen levels) prevent this. We studied the effects of short-day photoperiods and melatonin on Harderian porphyrin concentrations. Methods: Intact, castrated, or pinealectomized hamsters of both sexes were exposed to long-day or short-day photoperiods. Intact or castrated hamsters were given melatonin injections in the morning or the afternoon, or were given beeswax pellets containing melatonin. After a variable period, Harderian glands were dissected and porphyrins were measured. Results: Prolonged short-day exposure (13 weeks) led to increased Harderian porphyrin concentrations and this rise was prevented by pinealectomy. The rise in Harderian porphyrins following short-day exposure was small, compared with that following castration. Short-day photoperiods also prevented the rise in porphyrin levels associated with castration and this effect was prevented by removal of the pineal. Melatonin injections, whether given in the morning or in the afternoon, had no effect on Harderian porphyrin concentration of castrated male hamsters. Continuous release melatonin pellets reduced the postcastrational rise in porphyrin levels in one experiment, while having no effect in another. In female hamster, neither short photoperiods nor melatonin pellets influenced Harderian porphyrin concentrations. Conclusions: These results suggested that a factor from the pineal gland helps maintain the low levels of porphyrin which are characteristic of male Harderian glands, despite the decrease in androgen levels which typically results from exposure to short days. Morning and afternoon injections of melatonin and continuous release melatonin pellets failed to resolve the question of whether this pineal factor is melatonin. Our results demonstrated that low male and high female porphyrin levels are maintained in Syrian hamsters, despite seasonal variations in the hormonal milieu, suggesting that these sexual differences are important for the (still unestablished) function of the Harderian glands in this species. © 1994 Wiley-Liss, Inc.     

Altered chromatin landscape in circulating T follicular helper and regulatory cells following grass pollen subcutaneous and sublingual immunotherapy

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