6533b822fe1ef96bd127d981

RESEARCH PRODUCT

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

Marie-aleth Lacaille-dubois

subject

InflammasomesT-Lymphocytesmedicine.medical_treatmentHerpes zosterPharmaceutical ScienceMonophosphoryl Lipid AAPCs antigen presenting cellsMiceCMI cell mediated immunity0302 clinical medicineDrug DiscoveryHerpes Zoster VaccineMedicineNSCLC non small cell lung carcinomaCancerImmunity CellularVaccines Synthetic0303 health sciencesImmunogenicityIl-2 interleukine 2HIV human immunodeficiency virusLipid A030220 oncology & carcinogenesisCytokinesMolecular MedicineDCs dendritic cellsNK natural killerAdjuvantTLR Toll-like receptorHerpes Zoster VaccineCD cluster of differentiationAntigen-Presenting CellsCTL cytotoxic T lymphocytesHZ herpes zosterMPL 3-deacylated monophosphoryl lipidVaccine adjuvantImmunoadjuvantArticleVZV varicella zoster virus03 medical and health sciencesImmune systemAdjuvants ImmunologicAntigenPAMPs pathogen-associated molecular patternsMalaria VaccinesPRRs pathogen recognition receptorsQS-21 Quillaja saponaria Molina-fraction 21AnimalsMHC major histocompatibility complexMtb Mycobacterium tuberculosis bacteriaSARS severe acute respiratory syndromeAntigen-presenting cellIFN-γ interferon-gamma030304 developmental biologyPharmacologybusiness.industryA-β amyloid-betaTNF-α tumor necrosis factor-alphaSaponinsQS-21MalariaQuillaja saponariaComplementary and alternative medicineTCR T-cell receptorLiposomesImmunologyKLH keyhole limpet hemocyaninbusinessdLN draining lymph nodesMAPK mitogen activated protein kinase

description

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.

yearjournalcountryeditionlanguage
2019-07-01Phytomedicine
https://doi.org/10.1016/j.phymed.2019.152905