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Updated insights into the mechanism of action and clinical profile of the immunoadjuvant QS-21: A review
- Source :
- Phytomedicine
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
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.<br />Graphical abstract Image, graphical abstract
- Subjects :
- Inflammasomes
T-Lymphocytes
medicine.medical_treatment
Herpes zoster
Pharmaceutical Science
Monophosphoryl Lipid A
APCs, antigen presenting cells
Mice
CMI, cell mediated immunity
0302 clinical medicine
Drug Discovery
Herpes Zoster Vaccine
Medicine
NSCLC, non small cell lung carcinoma
Cancer
Immunity, Cellular
Vaccines, Synthetic
0303 health sciences
Immunogenicity
Il-2, interleukine 2
HIV, human immunodeficiency virus
Lipid A
030220 oncology & carcinogenesis
Cytokines
Molecular Medicine
DCs, dendritic cells
NK, natural killer
Adjuvant
TLR, Toll-like receptor
CD, cluster of differentiation
Antigen-Presenting Cells
CTL, cytotoxic T lymphocytes
HZ, herpes zoster
MPL, 3-deacylated monophosphoryl lipid
Vaccine adjuvant
Immunoadjuvant
Article
VZV, varicella zoster virus
03 medical and health sciences
Immune system
Adjuvants, Immunologic
Antigen
PAMPs, pathogen-associated molecular patterns
Malaria Vaccines
PRRs, pathogen recognition receptors
QS-21, Quillaja saponaria Molina-fraction 21
Animals
MHC, major histocompatibility complex
Mtb, Mycobacterium tuberculosis bacteria
SARS, severe acute respiratory syndrome
Antigen-presenting cell
IFN-γ, interferon-gamma
030304 developmental biology
Pharmacology
business.industry
A-β, amyloid-beta
TNF-α, tumor necrosis factor-alpha
Saponins
QS-21
Malaria
Quillaja saponaria
Complementary and alternative medicine
TCR, T-cell receptor
Liposomes
Immunology
KLH, keyhole limpet hemocyanin
business
dLN, draining lymph nodes
MAPK, mitogen activated protein kinase
Subjects
Details
- ISSN :
- 09447113
- Volume :
- 60
- Database :
- OpenAIRE
- Journal :
- Phytomedicine
- Accession number :
- edsair.doi.dedup.....f1e8eaac1d390e7eecaaa9b330b7a787