Different human vaccine adjuvants promote distinct antigen-independent immunological signatures tailored to different pathogens.
Different human vaccine adjuvants promote distinct antigen-independent immunological signatures tailored to different pathogens.
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DOI：
10.1038/srep19570
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发表时间：
2016-01-21
影响因子：
4.6
通讯作者：
Agger EM
中科院分区：
文献类型：
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作者：
Knudsen NP;Olsen A;Buonsanti C;Follmann F;Zhang Y;Coler RN;Fox CB;Meinke A;D'Oro U;Casini D;Bonci A;Billeskov R;De Gregorio E;Rappuoli R;Harandi AM;Andersen P;Agger EM
临床开发中的大多数候选疫苗都是高度纯化的蛋白质和肽，依靠佐剂来增强和/或直接免疫反应。尽管人们公认需要新型佐剂，但获得许可的人类疫苗中的佐剂仍然很少。大量佐剂已使用不同的实验条件进行了临床前测试，因此无法直接比较它们的活性。我们在小鼠体内对五种不同的佐剂 Alum、MF59®、GLA-SE、IC31® 和 CAF01 进行了头对头比较，并将它们与结核分枝杆菌、流感和衣原体的抗原结合起来，使用标准化方案测试感染模型中的免疫特征和功效。无论抗原如何，每种佐剂都具有独特的免疫学特征，表明佐剂具有针对不同疾病靶点的潜力。明矾增加抗体滴度； MF59® 诱导强烈的抗体和 IL-5 反应； GLA-SE诱导抗体和Th1； CAF01 显示出混合的 Th1/Th17 特征，IC31® 诱导强烈的 Th1 反应。 MF59® 和 GLA-SE 是流感 HI 滴度的强诱导剂，而 CAF01、GLA-SE 和 IC31® 增强了对结核病和衣原体的保护。重要的是，这是第一次根据免疫特征和保护功效对临床级佐剂进行分类的广泛尝试，为人类使用的下一代疫苗的合理开发提供信息。
The majority of vaccine candidates in clinical development are highly purified proteins and peptides relying on adjuvants to enhance and/or direct immune responses. Despite the acknowledged need for novel adjuvants, there are still very few adjuvants in licensed human vaccines. A vast number of adjuvants have been tested pre-clinically using different experimental conditions, rendering it impossible to directly compare their activity. We performed a head-to-head comparison of five different adjuvants Alum, MF59®, GLA-SE, IC31® and CAF01 in mice and combined these with antigens from M. tuberculosis, influenza, and chlamydia to test immune-profiles and efficacy in infection models using standardized protocols. Regardless of antigen, each adjuvant had a unique immunological signature suggesting that the adjuvants have potential for different disease targets. Alum increased antibody titers; MF59® induced strong antibody and IL-5 responses; GLA-SE induced antibodies and Th1; CAF01 showed a mixed Th1/Th17 profile and IC31® induced strong Th1 responses. MF59® and GLA-SE were strong inducers of influenza HI titers while CAF01, GLA-SE and IC31® enhanced protection to TB and chlamydia. Importantly, this is the first extensive attempt to categorize clinical-grade adjuvants based on their immune profiles and protective efficacy to inform a rational development of next generation vaccines for human use.