About: Updated insights into the mechanism of action and clinical profile of the immunoadjuvant QS-21: A review

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Updated insights into the mechanism of action and clinical profile of the immunoadjuvant QS-21: A review
Creator	Lacaille-Dubois, Marie-Aleth
topic	covid:2311677b6bab8221ee5d403f9f5de32fad8ec229#this
source	Elsevier; Medline; PMC
abstract	Abstract Background Vaccine adjuvants are compounds that significantly enhance/prolong the immune response to a co-administered antigen. The limitations of the use of aluminium salts that are unable to elicite cell responses against intracellular pathogens such as those causing malaria, tuberculosis, or AIDS, have driven the development of new alternative adjuvants such as QS-21, a triterpene saponin purified from Quillaja saponaria. Purpose The aim of this review is to attempt to clarify the mechanism of action of QS-21 through either receptors or signaling pathways in vitro and in vivo with special emphasis on the co-administration with other immunostimulants in new adjuvant formulations, called adjuvant systems (AS). Furthermore, the most relevant clinical applications will be presented. Methods A literature search covering the period 2014–2018 was performed using electronic databases from Sci finder, Science direct, Medline/Pubmed, Scopus, Google scholar. Results Insights into the mechanism of action of QS-21 can be summarized as follows: 1) in vivo stimulation of Th2 humoral and Th1 cell-mediated immune responses through action on antigen presenting cells (APCs) and T cells, leading to release of Th1 cytokines participating in the elimination of intracellular pathogens. 2) activation of the NLRP3 inflammasome in mouse APCs with subsequent release of caspase-1 dependent cytokines, Il-1β and Il-18, important for Th1 responses. 3) synthesis of nearly 50 QS-21 analogs, allowing structure/activity relationships and mechanistic studies. 4) unique synergy mechanism between monophosphoryl lipid A (MPL A) and QS-21, formulated in a liposome (AS01) in the early IFN-γ response, promoting vaccine immunogenicity. The second part of the review is related to phase I-III clinical trials of QS-21, mostly formulated in ASs, to evaluate efficacy, immunogenicity and safety of adjuvanted prophylactic vaccines against infectious diseases, e.g. malaria, herpes zoster, tuberculosis, AIDS and therapeutic vaccines against cancer and Alzheimer's disease. Conclusion The most advanced phase III clinical applications led to the development of two vaccines containing QS-21 as part of the AS, the Herpes Zoster vaccine (HZ/su) (Shingrix™) which received a license in 2017 from the FDA and a marketing authorization in the EU in 2018 and the RTS,S/AS01 vaccine (Mosquirix™) against malaria, which was approved by the EMA in 2015 for further implementation in Sub-Saharan countries for routine use.
has issue date	2019-07-31(xsd:dateTime)
bibo:doi	10.1016/j.phymed.2019.152905
bibo:pmid	31182297
has license	els-covid
sha1sum (hex)	2311677b6bab8221ee5d403f9f5de32fad8ec229
schema:url	https://doi.org/10.1016/j.phymed.2019.152905
resource representing a document's title	Updated insights into the mechanism of action and clinical profile of the immunoadjuvant QS-21: A review
has PubMed Central identifier	PMC7127804
has PubMed identifier	31182297
schema:publication	Phytomedicine
resource representing a document's body	covid:2311677b6bab8221ee5d403f9f5de32fad8ec229#body_text
is http://vocab.deri.ie/void#inDataset of	proxy:http/ns.inria.fr/covid19/2311677b6bab8221ee5d403f9f5de32fad8ec229
is schema:about of	named entity 'Conclusion' named entity 'special' named entity 'antigen' named entity 'salts' named entity 'immunoadjuvant' »more»

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