Cellular and molecular synergy in AS01-adjuvanted vaccines results in an early IFNγ response promoting vaccine immunogenicity.
Cellular and molecular synergy in AS01-adjuvanted vaccines results in an early IFNγ response promoting vaccine immunogenicity.
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DOI：
10.1038/s41541-017-0027-3
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发表时间：
2017
期刊：
影响因子：
9.2
通讯作者：
Didierlaurent AM
中科院分区：
文献类型：
--
作者：
Coccia M;Collignon C;Hervé C;Chalon A;Welsby I;Detienne S;van Helden MJ;Dutta S;Genito CJ;Waters NC;Deun KV;Smilde AK;Berg RAVD;Franco D;Bourguignon P;Morel S;Garçon N;Lambrecht BN;Goriely S;Most RV;Didierlaurent AM
在佐剂中结合免疫刺激剂可以改善对疫苗的免疫应答的质量。在这里，我们报告了TLR 4配体，3-O-脱酰基-4 '-单磷酰脂质A（MPL）和皂苷，QS-21，佐剂系统AS 01的成分之间的分子和细胞协同作用的独特机制。AS 01是疟疾和带状疱疹候选疫苗的一部分，已在III期研究中证明有效。注射AS 01佐剂疫苗后数小时，驻留细胞（如NK细胞和CD 8 + T细胞）在引流注射部位的淋巴结中释放IFNγ。这种作用由MPL和QS-21协同作用产生，并由巨噬细胞、IL-12和IL-18控制。耗尽策略表明，这种早期IFNγ的产生对于树突状细胞的活化和AS 01佐剂疫苗的Th 1免疫的发展是必需的。在注射AS 01的猕猴的淋巴结以及接受疟疾RTS，S疫苗的个体的血液中观察到类似的活化。这种机制，以前描述的感染，说明佐剂如何触发自然发生的途径，以提高疫苗的效力。揭示了一种机制，通过该机制，疫苗组分合作刺激免疫系统并提高疫苗效力。一些疫苗是用免疫剂配制的，这些化合物诱导对疫苗的更大免疫反应，并有助于引起对未来感染的更大保护。比利时GSK疫苗公司的Arnaud Didierlaurent和他的研究小组证明，在最近开发的几种疫苗中使用的佐剂AS 01中的两种免疫刺激剂协同作用，触发重要的免疫系统调节剂的激活。免疫刺激剂的协同作用调节疫苗接种部位的特异性免疫细胞，以更好地为身体对抗未来感染做好准备。这样的研究使我们能够更好地了解疫苗的工作原理，并为未来疫苗开发的更明智研究奠定基础。
Combining immunostimulants in adjuvants can improve the quality of the immune response to vaccines. Here, we report a unique mechanism of molecular and cellular synergy between a TLR4 ligand, 3-O-desacyl-4’-monophosphoryl lipid A (MPL), and a saponin, QS-21, the constituents of the Adjuvant System AS01. AS01 is part of the malaria and herpes zoster vaccine candidates that have demonstrated efficacy in phase III studies. Hours after injection of AS01-adjuvanted vaccine, resident cells, such as NK cells and CD8+ T cells, release IFNγ in the lymph node draining the injection site. This effect results from MPL and QS-21 synergy and is controlled by macrophages, IL-12 and IL-18. Depletion strategies showed that this early IFNγ production was essential for the activation of dendritic cells and the development of Th1 immunity by AS01-adjuvanted vaccine. A similar activation was observed in the lymph node of AS01-injected macaques as well as in the blood of individuals receiving the malaria RTS,S vaccine. This mechanism, previously described for infections, illustrates how adjuvants trigger naturally occurring pathways to improve the efficacy of vaccines. A mechanism is revealed by which vaccine components co-operate to stimulate the immune system and improve vaccine efficacy. Some vaccines are formulated with adjuvants—compounds that induce a greater immune response to the vaccine and help to elicit greater protection against future infections. Arnaud Didierlaurent and his team of researchers at GSK Vaccines, Belgium, demonstrate that the two immunostimulants in the adjuvant AS01, used in several recently developed vaccines, works in tandem to trigger the activation of important immune system moderators. The synergistic effect of the immunostimulants modulate specific immune cells at the site of the vaccination to better prepare the body against future infection. Studies such as this allow us to better understand how vaccines work and lay the foundation for more informed research into future vaccine development.
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影响因子：
5.5
作者：
Leroux-Roels, Isabel;Forgus, Sheron;Ofori-Anyinam, Opokua
通讯作者：
Ofori-Anyinam, Opokua
影响因子：
4.6
作者：
Detienne S;Welsby I;Collignon C;Wouters S;Coccia M;Delhaye S;Van Maele L;Thomas S;Swertvaegher M;Detavernier A;Elouahabi A;Goriely S;Didierlaurent AM
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Didierlaurent AM
影响因子：
4.4
作者：
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通讯作者：
Riley, Eleanor M.
影响因子：
56.9
作者：
HUANG, S;HENDRIKS, W;AGUET, M
通讯作者：
AGUET, M
影响因子：
20.3
作者：
Fehniger, TA;Cooper, MA;Caligiuri, MA
通讯作者：
Caligiuri, MA