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分析了皮内接种分剂量的萨宾灭活脊髓灰质炎病毒疫苗(sIPV)在大鼠中的免疫原性。

Analyzed immunogenicity of fractional doses of Sabin-inactivated poliovirus vaccine (sIPV) with intradermal delivery in rats.

作者信息

Ma Lei, Cai Wei, Sun Mingbo, Cun Yina, Zhou Jian, Liu Jing, Hu Wenzhu, Zhang Xinwen, Song Shaohui, Jiang Shude, Liao Guoyang

机构信息

a The Fifth Department of Biological Products , Institute of Medical Biology, Chinese Academy of Medical Science, Peking Union Medical College , Kunming , Yunnan Province , People's Republic of China.

出版信息

Hum Vaccin Immunother. 2016 Dec;12(12):3125-3131. doi: 10.1080/21645515.2016.1214347. Epub 2016 Aug 15.

Abstract

The live-attenuated oral polio vaccine (OPV) will be no longer used when wild poliovirus (WPV) eliminating in worldwide, according to GPEI (the Global Polio Eradication Initiative) Reports. It is planning to replace OPV by Sabin-based inactivated poliovirus vaccine (sIPV) in developing countries, with purpose of reducing of the economic burden and maintaining of the appropriate antibody levels in population. It studied serial fractional doses immunized by intradermal injection (ID) in rats, to reduce consume of antigen and financial burden, maintaining sufficient immunogenicity; Methods: Study groups were divided in 4 groups of dose gradient, which were one-tenth (1/10), one-fifth (1/5), one-third (1/3) and one-full dose (1/1), according to the volume of distribution taken from the same batch of vaccine (sIPV). Wistar rats were injected intradermally with the needle and syringe sing the mantoux technique taken once month for 3 times. It was used as positive control that intramuscular inoculation (IM) was injected with one-full dose (1/1) with same batch of sIPV. PBS was used as negative control. Blood samples were collected via tail vein. After 30 d with 3 round of immunization, it analyzed the changes of neutralization antibody titers in the each group by each immunization program end; Results: The results of seroconversion had positive correlation with different doses in ID groups. The higher concentration of D-antigen (D-Ag) could conduct higher seroconversion. Furthermore, different types of viruses had different seroconversion trend. It showed that the geometric mean titers (GMTs) of each fractional-dose ID groups increased by higher concentration of D-Ag, and it got significant lower than the full-dose IM group. At 90 days of immunization, the GMTs for each poliovirus subtypes of fractional doses were almost higher than 1:8, implied that it could be meaning positive seroprotection titer for polio vaccine types, according to WHO suggestion; Conclusions: The fractional dose with one-fifth (1/5) could be used by intradermal injection to prevent poliovirus infection, if there were more human clinical detail research consistent with this findings in rats.

摘要

根据全球消灭脊髓灰质炎行动(GPEI)的报告,当全球范围内消灭野生脊髓灰质炎病毒(WPV)后,减毒口服脊髓灰质炎疫苗(OPV)将不再使用。该行动计划在发展中国家用基于萨宾株的灭活脊髓灰质炎病毒疫苗(sIPV)替代OPV,以减轻经济负担并维持人群中适当的抗体水平。研究通过皮内注射(ID)对大鼠进行系列分剂量免疫,以减少抗原消耗和经济负担,同时维持足够的免疫原性;方法:根据同一批次疫苗(sIPV)的分配体积,将研究组分为4个剂量梯度组,分别为十分之一(1/10)、五分之一(1/5)、三分之一(1/3)和全剂量(1/1)。采用曼托试验技术,用针头和注射器每月对Wistar大鼠进行1次皮内注射,共注射3次。用同一批次sIPV全剂量(1/1)进行肌肉注射(IM)作为阳性对照。用PBS作为阴性对照。通过尾静脉采集血样。在3轮免疫后30天,在每个免疫程序结束时分析每组中和抗体滴度的变化;结果:ID组的血清转化结果与不同剂量呈正相关。较高浓度的D抗原(D-Ag)可导致较高的血清转化率。此外,不同类型的病毒有不同的血清转化趋势。结果显示,各分剂量ID组的几何平均滴度(GMT)随D-Ag浓度升高而增加,但显著低于全剂量IM组。在免疫90天时,各分剂量脊髓灰质炎病毒亚型的GMT几乎均高于1:8,根据世界卫生组织的建议,这意味着对脊髓灰质炎疫苗类型可能具有阳性血清保护滴度;结论:如果在人体临床有更多与大鼠研究结果一致的详细研究,五分之一(1/5)分剂量可用于皮内注射预防脊髓灰质炎病毒感染。

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