Cellular and molecular synergy in AS01-adjuvanted vaccines results in an early IFNγ response promoting vaccine immunogenicity

被引：188

作者：

Coccia, Margherita ^{[1
]}

Collignon, Catherine ^{[1
]}

Herve, Caroline ^{[1
]}

Chalon, Aurelie ^{[1
]}

Welsby, Iain ^{[2
]}

Detienne, Sophie ^{[2
]}

van Helden, Mary J. ^{[3
]}

Dutta, Sheetij ^{[4
]}

Genito, Christopher J. ^{[4
]}

Waters, Norman C. ^{[4
]}

Van Deun, Katrijn ^{[5
,6
]}

Smilde, Age K. ^{[7
]}

van den Berg, Robert A. ^{[1
]}

Franco, David ^{[1
]}

Bourguignon, Patricia ^{[1
]}

Morel, Sandra ^{[1
]}

Garcon, Nathalie ^{[1
]}

Lambrecht, Bart N. ^{[3
]}

Goriely, Stanislas ^{[2
]}

van der Most, Robbert ^{[1
]}

Didierlaurent, Arnaud M. ^{[1
]}

机构：

[1] IGSK Vaccines, Rixensart, Belgium

[2] Univ Libre Bruxelles, Inst Med Immunol, Gosselies, Belgium

[3] Univ Ghent, Inflammat Res Ctr, Vlaams Inst Biotechnol, Ghent, Belgium

[4] Walter Reed Army Inst Res, Mil Malaria Res Program, Malaria Vaccine Branch, Silver Spring, MD USA

[5] Tilburg Univ, Dept Methodol & Stat, Tilburg, Netherlands

[6] Katholieke Univ Leuven, Dept Psychol, Leuven, Belgium

[7] Univ Amsterdam, Swammerdam Inst Life Sci, Biosyst Data Anal, Amsterdam, Netherlands

来源：

NPJ VACCINES | 2017年 / 2卷

关键词：

FALCIPARUM CIRCUMSPOROZOITE PROTEIN; NK CELLS; T-CELLS; IMMUNE-RESPONSE; DENDRITIC CELLS; LYMPH-NODES; INFLUENZA VACCINATION; HOST-DEFENSE; MICE; PROTECTION;

D O I：

10.1038/s41541-017-0027-3

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 IFN. 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 IFN. 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.

引用

页数：14

共 49 条

[21] A Spatially-Organized Multicellular Innate Immune Response in Lymph Nodes Limits Systemic Pathogen Spread [J].