Co-delivery of amphipol-conjugated adjuvant with antigen, and adjuvant combinations, enhance immune protection elicited by a membrane protein-based vaccine against a mucosal challenge with Chlamydia.
Co-delivery of amphipol-conjugated adjuvant with antigen, and adjuvant combinations, enhance immune protection elicited by a membrane protein-based vaccine against a mucosal challenge with Chlamydia.
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两性醇缀合佐剂与抗原以及佐剂组合的共同递送增强了基于膜蛋白的疫苗针对衣原体粘膜攻击所引发的免疫保护。
DOI：
10.1016/j.vaccine.2018.09.055
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发表时间：
2018
期刊：
影响因子：
5.5
通讯作者：
delaMaza,LuisM
中科院分区：
文献类型：
--
作者：
Tifrea,DeliaF;Pal,Sukumar;LeBon,Christel;Giusti,Fabrice;Popot,Jean-Luc;Cocco,MelanieJ;Zoonens,Manuela;delaMaza,LuisM
简介衣原体感染在世界范围内传播，需要疫苗来控制这种病原体。本研究的目的是确定通过衍生化的 amphipol 传递与抗原相关的佐剂以及佐剂组合是否可以改善疫苗保护。方法使用了一种新颖的方法，即用带有共价缀合肽 (EP67) 的 amphipol (A8-35) 捕获鼠衣原体 (Cm) 天然 MOMP (nMOMP)。掺入的佐剂为： EP67 与 A8-35 缀合，用于捕获 nMOMP (nMOMP/EP67-A8-35)，或游离作为对照，添加到 nMOMP/A8-35 复合物中 (nMOMP/A8-35+EP67)； Montanide ISA 720 可增强体液反应，CpG-1826 可引发强大的细胞介导免疫 (CMI)。 BALB/c小鼠通过粘膜和全身途径免疫。使用liveCm鼻内免疫作为阳性对照，并包括三个阴性对照。对小鼠进行鼻内攻击，并评估体重、肺重量和从肺中回收的Cm包含物形成单位(IFU)数量的变化以建立保护作用。为了评估肺上清液中 IFN-γ 和 Cm 特异性 IgA 的局部反应水平。结果结构测定表明，当 A8-35 被共价修饰时，nMOMP 二级结构和热稳定性得以保持。接种 nMOMP/EP67-A8-35 的小鼠比接种 nMOMP/A8-35+EP67 的动物受到更好的保护。添加 Montanide 可增强 Th2 反应并改善保护。包括 CpG-1826 进一步扩大、强化并转向 Th1 偏向的免疫反应。根据体重、肺重量和从肺中回收的 IFU 数量的变化确定，随着 nMOMP 和三种佐剂的递送，攻击后 10 天的保护作用相当于使用 liveCm 免疫诱导的保护作用。 结论 EP67 与 A8-35 的共价结合用于保持 nMOMP 水溶性，比游离 EP67 所提供的保护作用提高。包括EP67+Montanide+CpG-1826在内的佐剂组合，通过扩大和强化细胞和体液免疫反应，进一步增强保护。
IntroductionChlamydial infections are spread worldwide and a vaccine is needed to control this pathogen. The goals of this study were to determine if the delivery of an adjuvant associated to the antigen, via a derivatized amphipol, and adjuvant combinations improve vaccine protection.MethodsA novel approach, trapping the Chlamydia muridarum (Cm) native MOMP (nMOMP) with amphipols (A8-35), bearing a covalently conjugated peptide (EP67), was used. Adjuvants incorporated were: EP67 either conjugated to A8-35, which was used to trap nMOMP (nMOMP/EP67-A8-35), or free as a control, added to nMOMP/A8-35 complexes (nMOMP/A8-35+EP67); Montanide ISA 720 to enhance humoral responses, and CpG-1826 to elicit robust cell-mediated immunity (CMI). BALB/c mice were immunized by mucosal and systemic routes. Intranasal immunization with liveCmwas used as positive control and three negative controls were included. Mice were challenged intranasally withCmand changes in body weight, lungs weight and number ofCm-inclusion forming units (IFU) recovered from the lungs were evaluated to establish protection. To assess local responses levels of IFN- γ andCm-specific IgA were determined in lungs’ supernatants.ResultsStructural assays demonstrated that nMOMP secondary structure and thermal stability were maintained when A8-35 was covalently modified. Mice vaccinated with nMOMP/EP67-A8-35 were better protected than animals immunized with nMOMP/A8-35+EP67. Addition of Montanide enhanced Th2 responses and improved protection. Including CpG-1826 further broadened, intensified and switched to Th1-biased immune responses. With delivery of nMOMP and the three adjuvants, as determined by changes in body weight, lungs weight and number of IFU recovered from lungs, protection at 10 days post-challenge was equivalent to that induced by immunization with liveCm.ConclusionsCovalent association of EP67 to A8-35, used to keep nMOMP water-soluble, improves protection over that conferred by free EP67. Adjuvant combinations including EP67+Montanide+CpG-1826, by broadening and intensifying cellular and humoral immune responses, further enhanced protection.