Use of a Clostridioides difficile Murine Immunization and Challenge Model to Evaluate Single and Combination Vaccine Adjuvants Consisting of Alum and NKT Cell-Activating Ligands.
Use of a Clostridioides difficile Murine Immunization and Challenge Model to Evaluate Single and Combination Vaccine Adjuvants Consisting of Alum and NKT Cell-Activating Ligands.
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DOI：
10.3389/fimmu.2021.818734
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发表时间：
2021
影响因子：
7.3
通讯作者：
Lang ML
中科院分区：
文献类型：
--
作者：
Lang GA;Norman K;Amadou Amani S;Shadid TM;Ballard JD;Lang ML
佐剂组合可以增强或扩大对疫苗抗原的免疫应答的表达。目前缺乏关于已建立的明矾型佐剂是否可以与实验性CD 1d配体佐剂组合的信息。在本研究中，我们使用鼠艰难梭菌免疫和攻击模型来评估明矾（Alhydrogel™）、α-半乳糖神经酰胺（α-GC）及其类似物之一7 DW 8 -5单独和组合作为疫苗佐剂。我们观察到，明矾/α-GC组合导致疫苗抗原特异性IgG 1和IgG 2b应答适度增强，并扩大至包括IgG 2c，但对总体保护无显著影响。使用明矾/7 DW 8 -5组合进行了类似的观察。佐剂对NKT细胞的影响的检查揭示了不变NKT（iNKT）细胞的扩增，其iNKTfh亚群适度扩增，并且对不同NKT（dNKT）细胞几乎没有影响。测定了佐剂的副作用，当明矾/α-GC联合使用而不是单独使用时，显示短暂的肝毒性。总之，这些结果表明，明矾/α-GC或明矾/7 DW 8 -5组合可对NKT细胞区室和同种型转换产生不同的影响，以产生除明矾/Th 2驱动的亚类之外的Th 1驱动的IgG亚类。单独使用明矾可有效刺激IgG介导的保护作用，而α-GC在C.艰难梭菌攻击模型，本文的工作揭示了可以在其他疫苗背景下优化和利用的免疫应答特征。
Adjuvant combinations may enhance or broaden the expression of immune responses to vaccine antigens. Information on whether established Alum type adjuvants can be combined with experimental CD1d ligand adjuvants is currently lacking. In this study, we used a murine Clostridioides difficile immunization and challenge model to evaluate Alum (Alhydrogel™), α-galactosylceramide (α-GC), and one of its analogs 7DW8-5 singly and in combination as vaccine adjuvants. We observed that the Alum/α-GC combination caused modest enhancement of vaccine antigen-specific IgG1 and IgG2b responses, and a broadening to include IgG2c that did not significantly impact overall protection. Similar observations were made using the Alum/7DW8-5 combination. Examination of the impact of adjuvants on NKT cells revealed expansion of invariant NKT (iNKT) cells with modest expansion of their iNKTfh subset and little effect on diverse NKT (dNKT) cells. Side effects of the adjuvants was determined and revealed transient hepatotoxicity when Alum/α-GC was used in combination but not singly. In summary these results showed that the Alum/α-GC or the Alum/7DW8-5 combination could exert distinct effects on the NKT cell compartment and on isotype switch to produce Th1-driven IgG subclasses in addition to Alum/Th2-driven subclasses. While Alum alone was efficacious in stimulating IgG-mediated protection, and α-GC offered no apparent additional benefit in the C. difficile challenge model, the work herein reveals immune response features that could be optimized and harnessed in other vaccine contexts.
影响因子：
15.3
作者：
HAYAKAWA, K;LIN, BT;HARDY, RR
通讯作者：
HARDY, RR
DOI：
10.4049/jimmunol.1300263
发表时间：
2013-08-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Shah HB;Joshi SK;Rampuria P;Devera TS;Lang GA;Stohl W;Lang ML
通讯作者：
Lang ML