【作者】 常娅莉； 吴智远； 祁芝珍； 焦磊； 韩少波； 戴瑞霞； 胡丽娜； 卜培英； 王秉翔；

【机构】 兰州生物制品研究所有限责任公司； 青海省地方病预防控制所；

【摘要】 我们研制了新型鼠疫基因工程疫苗,疫苗是由鼠疫菌培养液中提取天然F1抗原与重组鼠疫菌rV抗原配伍,以氢氧化铝为吸附剂而组成的基因工程疫苗,对疫苗的各种理化指标,按"《中国药典》2005年版二部原料药与药物制剂稳定性试验指导原则"进行检定,各项指标均符合规程要求。鼠疫疫苗属对温度特别敏感的药物制剂,本文重点讨论对临床试验申请用样品鼠疫疫苗20081002,20081003,20081004三批制品,进行加速稳定性试验,将疫苗在温度25℃±2℃、相对湿度60%±10%的条件下,倒立放置6个月;长期稳定性试验,将疫苗在温度6℃±2℃的条件下,倒立放置3、6、9、12、18、24个月,对鼠疫基因工程疫苗免疫力和保护力以及各项生物生化指标进行为期24个月的试验观察,同时在25℃及6℃±2℃保存6个月条件下免疫动物,进行免疫效价测定,计算几何平均数≥1:2000,为合格。利用双抗体夹心法测定疫苗成分中的F1抗原和V抗原。同时用该疫苗在25℃保存6个月条件下及6℃保存6个月、9个月、12个月免疫豚鼠,第4W后,用鼠疫EV菌强毒株进行攻击,计算豚鼠的保护力。结果表明,F1+V抗原+AI(OH)3佐剂配制的鼠疫基因工程疫苗有稳定的免疫力和保护力,就目前所做的这些试验可以说明该疫苗是一种理想的新型亚单位基因疫苗,有望早日替代老的鼠疫活疫苗。更多还原

【Abstract】 We constructed a new plague genetically engineered vaccine,which were combined with pestis natural F1 antigen,recombinant V antigen and adjuvant aluminum hydroxide as adsorbent.We had observed the Immune response,Protective efficacy and various biochemical indicators of the new plague genetically engineered vaccine for 24 months.First,NIH mice were divided into five groups and were immunized respectively with the new vaccine which were stored at 6℃ for 3 month,6month,9 month,12 month ,18 month of 24 month .Mice were bled for the detection of serum antibodies using ELISA between 2W and 4W after the second inoculation,and then determined the immune titers and calculated the the geometric mean of all samples.In addition,we immunized the mice with vaccines that stored at 6℃ for 6 month,9 month,12 month ,18 month of 24 month .or at 25℃for 6 month respectively and determined the immune titers and calculated the the geometric mean and the sample titer which ≥1:2000 was considered as qualified.Finally,we immunized guinea pigs with vaccines that were stored at 6 ℃ for6month,9 month,12 month or the vaccine stored at 25℃ for 6month separately,all groups were challenged with pestis EV at 4th weeks after inoculation and Protection was assayed.The results showed that this new plague genetically engineered vaccine had perfect immune response and protective efficacy,and all the indicators corresponded with the vaccine standards.It indicates that this vaccine is an ideal new subunit genetic vaccine and would replace the old live pestis vaccine.guinea pigs更多还原