Production and efficacy of a low-cost recombinant pneumococcal protein polysaccharide conjugate vaccine.
Production and efficacy of a low-cost recombinant pneumococcal protein polysaccharide conjugate vaccine.
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DOI：
10.1016/j.vaccine.2018.05.036
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发表时间：
2018-06-18
期刊：
影响因子：
5.5
通讯作者：
Mitchell TJ
中科院分区：
文献类型：
--
作者：
Herbert JA;Kay EJ;Faustini SE;Richter A;Abouelhadid S;Cuccui J;Wren B;Mitchell TJ
大肠杆菌生产的肺炎球菌糖结合疫苗对小鼠具有保护作用。保护作用与声速抗体水平相关。这是一种更便宜的生产结合疫苗的方法。肺炎链球菌是引起细菌性肺炎的主要原因。尽管这是一种可通过疫苗预防的疾病，但肺炎链球菌每年仍造成100多万人死亡，主要是5岁以下儿童。最大的疾病负担发生在发展中国家，这主要是由于疫苗价格高昂而无法获得。蛋白多糖结合疫苗在发达国家常规给予儿童，以诱导对肺炎链球菌的保护性抗体反应。其中一种疫苗是Prevnar13，它针对95种已知荚膜类型中的13种。目前的疫苗生产需要大量培养13种血清型，并分离荚膜多糖，然后通过一个昂贵的多步骤程序将其化学偶联到蛋白质上，例如白喉类毒素CRM197。本研究在大肠杆菌中设计、纯化和生产新型重组肺炎球菌蛋白多糖结合疫苗，作为低成本生产结合疫苗的微型工厂。重组疫苗在肺炎球菌肺炎小鼠模型上的有效性进行了测试；预防侵袭性疾病的能力与Prevnar13比较。本研究首次从原理上证明了大肠杆菌蛋白多糖结合疫苗可用于预防肺炎球菌感染。以这种方式生产的疫苗可能是目前疫苗生产方法的一种低成本替代方法。
Pneumococcal glycoconjugate vaccines produced in E. coli are protective in mice. Protection correlates with opsonic antibody levels. This is a cheaper way to produce conjugate vaccines. Streptococcus pneumoniae is the leading cause of bacterial pneumonia. Although this is a vaccine preventable disease, S. pneumoniae still causes over 1 million deaths per year, mainly in children under the age of five. The biggest disease burden is in the developing world, which is mainly due to unavailability of vaccines due to their high costs. Protein polysaccharide conjugate vaccines are given routinely in the developed world to children to induce a protective antibody response against S. pneumoniae. One of these vaccines is Prevnar13, which targets 13 of the 95 known capsular types. Current vaccine production requires growth of large amounts of the 13 serotypes, and isolation of the capsular polysaccharide that is then chemically coupled to a protein, such as the diphtheria toxoid CRM197, in a multistep expensive procedure. In this study, we design, purify and produce novel recombinant pneumococcal protein polysaccharide conjugate vaccines in Escherichia coli, which act as mini factories for the low-cost production of conjugate vaccines. Recombinant vaccine efficacy was tested in a murine model of pneumococcal pneumonia; ability to protect against invasive disease was compared to that of Prevnar13. This study provides the first proof of principle that protein polysaccharide conjugate vaccines produced in E. coli can be used to prevent pneumococcal infection. Vaccines produced in this manner may provide a low-cost alternative to the current vaccine production methodology.
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影响因子：
3.1
作者：
Cohen, D;Ashkenazi, S;Robbins, JB
通讯作者：
Robbins, JB
影响因子：
15.3
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Goebel, WF
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9.4
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Kirkham, LAS;Jefferies, JMC;Mitchell, TJ
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Mitchell, TJ
影响因子：
5.8
作者：
Kay EJ;Yates LE;Terra VS;Cuccui J;Wren BW
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影响因子：
6.4
作者：
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Ren Q