A recombinant conjugated pneumococcal vaccine that protects against murine infections with a similar efficacy to Prevnar-13.
A recombinant conjugated pneumococcal vaccine that protects against murine infections with a similar efficacy to Prevnar-13.
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DOI：
10.1038/s41541-018-0090-4
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发表时间：
2018
期刊：
影响因子：
9.2
通讯作者：
Brown JS
中科院分区：
文献类型：
--
作者：
Reglinski M;Ercoli G;Plumptre C;Kay E;Petersen FC;Paton JC;Wren BW;Brown JS
肺炎球菌结合疫苗（PCV）对疫苗血清型有很强的保护作用，但非疫苗血清型疾病的迅速蔓延和疫苗的高费用降低了其整体影响。我们开发了蛋白聚糖偶联技术（PGCT）作为一种灵活的方法，用于在大肠杆菌中重组制备低成本的多糖/蛋白糖缀合物。我们已经使用PGCT制备了含有与肺炎链球菌蛋白NanA、PiuA和Sp 0148连接的血清型4荚膜多糖的重组PCV。将空肠弯曲菌UDP-葡萄糖4-差向异构酶基因GalE（gne）导入E.大肠杆菌提高了所得糖蛋白的产率。PGCT糖缀合物疫苗接种在小鼠中产生对囊和载体蛋白抗原的强烈抗体应答，其中PiuA/囊糖缀合物诱导与商业PCV Prevnar-13类似的抗囊抗体应答。对PGCT糖缀合物调理的S. pneumoniae和表达血清型4荚膜的缓症链球菌，并促进中性粒细胞对S.肺炎链球菌的抗血清水平与通过用Prevnar-13接种产生的抗血清水平相似。用PGCT糖缀合物疫苗接种保护小鼠免受脑膜炎和败血症，其效力与用Prevnar-13疫苗接种相同。此外，单独使用PGCT糖缀合物的蛋白抗原组分接种疫苗可提供部分保护，防止败血症和定植。这些数据表明，由PGCT制备的疫苗与Prevnar-13一样有效，鉴定了PiuA作为糖缀合物疫苗的载体蛋白，并证明将荚膜抗原连接到S.肺炎球菌蛋白抗原具有额外的保护性益处，其可提供一定程度的非依赖型免疫。目前的肺炎球菌结合疫苗诱导对感染的保护性免疫，但这种保护仅限于制剂中包含的主要致病菌株。未纳入疫苗的新出现菌株未被覆盖，这限制了疫苗在与替代肺炎球菌菌株相关的地区的保护作用。在这里，Jeremy Brown，Brendan Wren及其同事优化并应用蛋白聚糖偶联技术来生产重组肺炎球菌多糖/蛋白糖缀合物，并在小鼠感染模型中对其进行评估。糖缀合物疫苗接种导致产生对胶囊和载体蛋白特异性的抗体，这导致在脑膜炎和败血症小鼠模型中的保护作用与目前使用的疫苗接种策略相当。这项动物研究强调了糖缀合物疫苗方法在肺炎球菌介导的疾病中的潜力。
The pneumococcal conjugate vaccine (PCV) strongly protects against vaccine serotypes, but the rapid expansion of non-vaccine serotype disease and the vaccine’s high expense has reduced its overall impact. We have developed Protein Glycan Coupling Technology (PGCT) as a flexible methodology for making low-cost polysaccharide/protein glycoconjugates recombinantly in Escherichia coli. We have used PGCT to make a recombinant PCV containing serotype 4 capsular polysaccharide linked to the Streptococcus pneumoniae proteins NanA, PiuA, and Sp0148. The introduction of the Campylobacter jejuni UDP-glucose 4-epimerase gene GalE (gne) into E. coli improved the yield of the resulting glycoprotein. PGCT glycoconjugate vaccination generated strong antibody responses in mice to both the capsule and the carrier protein antigens, with the PiuA/capsule glycoconjugate inducing similar anti-capsular antibody responses as the commercial PCV Prevnar-13. Antibody responses to PGCT glycoconjugates opsonised S. pneumoniae and Streptococcus mitis expressing the serotype 4 capsule and promoted neutrophil phagocytosis of S. pneumoniae to a similar level as antisera generated by vaccination with Prevnar-13. Vaccination with the PGCT glycoconjugates protected mice against meningitis and septicaemia with the same efficacy as vaccination with Prevnar-13. In addition, vaccination with the protein antigen components from PGCT glycoconjugates alone provided partial protection against septicaemia and colonisation. These data demonstrate that a vaccine made by PGCT is as effective as Prevnar-13, identifies PiuA as a carrier protein for glycoconjugate vaccines, and demonstrates that linking capsular antigen to S. pneumoniae protein antigens has additional protective benefits that could provide a degree of serotype-independent immunity. The current pneumococcal conjugate vaccine induces protective immunity to infection, but this protection is limited to the dominant disease-causing strains included in the preparation. Emerging strains not included in the vaccine are not covered, which limits the vaccine’s protective effect in areas associated with alternative pneumococcal strains. Here Jeremy Brown, Brendan Wren and colleagues have optimised and applied Protein Glycan Coupling Technology to produce recombinant pneumococcal polysaccharide/protein glycoconjugates and evaluated these in a murine model of infection. Glycoconjugate vaccination resulted in antibody production specific to both capsule and the carrier proteins, which resulted in protection in murine models of meningitis and septicaemia equivalent to that of currently used vaccination strategies. This animal study highlights the potential of glycoconjugate vaccine approaches in the context of pneumococcal mediated disease.
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影响因子：
9.3
作者：
Alari A;Chaussade H;Domenech De Cellès M;Le Fouler L;Varon E;Opatowski L;Guillemot D;Watier L
通讯作者：
Watier L
影响因子：
5.5
作者：
Cornick JE;Tastan Bishop Ö;Yalcin F;Kiran AM;Kumwenda B;Chaguza C;Govindpershad S;Ousmane S;Senghore M;du Plessis M;Pluschke G;Ebruke C;McGee L;Sigaùque B;Collard JM;Bentley SD;Kadioglu A;Antonio M;von Gottberg A;French N;Klugman KP;Heyderman RS;Alderson M;Everett DB;PAGe consortium
通讯作者：
PAGe consortium
影响因子：
4.3
作者：
Jervis AJ;Wood AG;Cain JA;Butler JA;Frost H;Lord E;Langdon R;Cordwell SJ;Wren BW;Linton D
通讯作者：
Linton D
影响因子：
3.1
作者：
Hyams, Catherine;Yuste, Jose;Brown, Jeremy S.
通讯作者：
Brown, Jeremy S.
DOI：
10.1073/pnas.0501254102
发表时间：
2005-03-29
影响因子：
11.1
作者：
Malley, R;Trzcinski, K;Lipsitch, M
通讯作者：
Lipsitch, M