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研究基于荚膜多糖的糖缀合物作为预防甲型流感嗜血杆菌疾病疫苗的适用性:满足未被满足的公共卫生需求的一种解决方案。

Investigating the candidacy of a capsular polysaccharide-based glycoconjugate as a vaccine to combat Haemophilus influenzae type a disease: A solution for an unmet public health need.

作者信息

Cox Andrew D, Williams Dean, Cairns Chantelle, St Michael Frank, Fleming Perry, Vinogradov Evgeny, Arbour Mélanie, Masson Luke, Zou Wei

机构信息

Vaccine Program, Human Health Therapeutics Portfolio, National Research Council, Ottawa, ON K1A 0R6, Canada.

Vaccine Program, Human Health Therapeutics Portfolio, National Research Council, Ottawa, ON K1A 0R6, Canada.

出版信息

Vaccine. 2017 Oct 27;35(45):6129-6136. doi: 10.1016/j.vaccine.2017.09.055. Epub 2017 Sep 23.

DOI:10.1016/j.vaccine.2017.09.055
PMID:28951087
Abstract

After the introduction of the glycoconjugate vaccine based upon the capsular polysaccharide ofHaemophilus influenzaetype b in the mid 1980s there was a remarkable decrease in the number of invasive cases reported for this organism. Since the 1990s several groups have observed the emergence ofHaemophilus influenzaetype a (Hia), especially in indigenous communities in the northern regions of Canada and Alaska, to a stage where a solution is warranted to prevent further unnecessary deaths due to this pathogen. A glycoconjugate vaccine solution based upon the type a capsular polysaccharide (CPS) was investigated pre-clinically in an effort to illustrate the proof of concept for this approach. In this study we describe the growth of Hia and the isolation, purification and conjugation of the CPS to several carrier proteins. The resulting glycoconjugates were immunised in mice and rabbits provoking sera that facilitated bactericidal killing against all type a strains that we tested. This study has illustrated the pre-clinical proof of concept of a glycoconjugate vaccine based on the CPS of Hia asa solution to this emerging disease.

摘要

20世纪80年代中期引入基于b型流感嗜血杆菌荚膜多糖的糖缀合物疫苗后,该病原体报告的侵袭性病例数量显著减少。自20世纪90年代以来,多个研究小组观察到a型流感嗜血杆菌(Hia)的出现,尤其是在加拿大北部和阿拉斯加的原住民社区,已到了需要采取解决方案以防止该病原体导致更多不必要死亡的阶段。基于a型荚膜多糖(CPS)的糖缀合物疫苗解决方案在临床前进行了研究,以阐明该方法的概念验证。在本研究中,我们描述了Hia的生长以及CPS与几种载体蛋白的分离、纯化和缀合。将所得糖缀合物在小鼠和兔子中免疫,激发的血清有助于对我们测试的所有a型菌株进行杀菌杀灭。本研究阐明了基于Hia CPS的糖缀合物疫苗作为这种新出现疾病解决方案的临床前概念验证。

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