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针对卡他莫拉菌和流感嗜血杆菌的截短脂寡糖-外膜蛋白结合疫苗的免疫特性。

Immunological characterisation of truncated lipooligosaccharide-outer membrane protein based conjugate vaccine against Moraxella catarrhalis and nontypeable Haemophilus influenzae.

机构信息

Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia; Institute for Glycomics, Griffith University, Gold Coast, Australia; School of Medical Science, Griffith University, Gold Coast, Australia.

Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia; School of Medical Science, Griffith University, Gold Coast, Australia.

出版信息

Vaccine. 2020 Jan 10;38(2):309-317. doi: 10.1016/j.vaccine.2019.10.014. Epub 2019 Oct 23.

Abstract

Moraxella catarrhalis and nontypeable Haemophilus influenzae are important bacterial causes of otitis media in children and respiratory diseases in adults. Lipooligosaccharide (LOS) from M. catarrhalis and outer membrane protein 26 (OMP26) from NTHi are major surface antigens identified as potential vaccine components against these organisms. We previously constructed M. catarrhalis in which LOS is truncated, but contains a structure common to the three known serotypes of M. catarrhalis. OMP26 is known to enhance clearance of NTHi following vaccination in animal models, so was chosen as the carrier protein. In this study, we conjugated wild-type and truncated M. catarrhalis detoxified-LOS to a recombinant modified OMP26, rOMP26VTAL. Vaccination of mice with these conjugates resulted in a significant increase in anti-LOS and anti-rOMP26VTAL IgG levels. Importantly, mouse antisera showed complement-mediated bactericidal activity against all M. catarrhalis serotype A and B strains and a NTHi strain tested. Serotypes A & B make up more than 90% of isolates. These data suggest that the LOS and OMP based conjugate can be used as vaccine components and require further investigation in animal models.

摘要

卡他莫拉菌和流感嗜血杆菌是非定型株是儿童中耳炎和成人呼吸道疾病的重要细菌病原体。卡他莫拉菌的脂寡糖(LOS)和无定型流感嗜血杆菌的外膜蛋白 26(OMP26)是主要的表面抗原,被认为是针对这些病原体的潜在疫苗成分。我们之前构建了 LOS 截短但含有三种已知卡他莫拉菌血清型共同结构的卡他莫拉菌。OMP26 已知在动物模型中接种后能增强对 NTHi 的清除作用,因此被选为载体蛋白。在这项研究中,我们将野生型和截短的卡他莫拉菌解毒 LOS 与重组改良 OMP26(rOMP26VTAL)缀合。用这些缀合物对小鼠进行免疫接种可显著增加抗 LOS 和抗 rOMP26VTAL IgG 水平。重要的是,小鼠抗血清对所有测试的 A 型和 B 型卡他莫拉菌菌株以及 NTHi 菌株显示出补体介导的杀菌活性。A 型和 B 型占分离株的 90%以上。这些数据表明,基于 LOS 和 OMP 的缀合物可用作疫苗成分,需要在动物模型中进一步研究。

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