Lysosome-Dependent Activation of Human Dendritic Cells by the Vaccine Adjuvant QS-21

Welsby, Iain; Detienne, Sophie; N’Kuli, Francisca; Thomas, Séverine; Wouters, Sandrine; Bechtold, Viviane; Wit, Dominique De; Gineste, Romain; Reinheckel, Thomas; Elouahabi, Abdelatif; Courtoy, Pierre J.; Didierlaurent, Arnaud M.; Goriely, Stanislas

doi:10.3389/fimmu.2016.00663

Cited by 69 publications

(100 citation statements)

References 59 publications

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“…In human monocyte-derived DCs (moDC), QS-21 (also a component of AS01) is endocytosed via the action of membrane cholesterol, with subsequent lysosomal destabilization and Syk activation to promote a pro-inflammatory transcription program. In addition, cathepsin B (a lysosomal cysteine protease) is required for activation of moDCs in vitro and also required for adjuvant activity of QS-21 in vivo [39]. In another study, LN-resident CD11b + CD169 + macrophages played a key role in the adjuvant activity of QS-21.…”

Section: Carbohydrate-based Adjuvantsmentioning

confidence: 98%

Selection of adjuvants for vaccines targeting specific pathogens

Sarkar

Garg

Hurk

2019

Expert Review of Vaccines

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Introduction: Adjuvants form an integral component in most of the inactivated and subunit vaccine formulations. Careful and proper selection of adjuvants helps in promoting appropriate immune responses against target pathogens at both innate and adaptive levels such that protective immunity can be elicited. Areas covered: Herein, we describe the recent progress in our understanding of the mode of action of adjuvants that are licensed for use in human vaccines or in clinical or pre-clinical stages at both innate and adaptive levels. Different pathogens have distinct characteristics, which require the host to mount an appropriate immune response against them. Adjuvants can be selected to elicit a tailor-made immune response to specific pathogens based on their unique properties. Identification of biomarkers of adjuvanticity for several candidate vaccines using omics-based technologies can unravel the mechanism of action of modern and experimental adjuvants. Expert opinion: Adjuvant technology has been revolutionized over the last two decades. In-depth understanding of the role of adjuvants in activating the innate immune system, combined with systems vaccinology approaches, have led to the development of next-generation, novel adjuvants that can be used in vaccines against challenging pathogens and in specific target populations. ARTICLE HISTORY

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Section: Carbohydrate-based Adjuvantsmentioning

confidence: 98%

Selection of adjuvants for vaccines targeting specific pathogens

Sarkar

Garg

Hurk

2019

Expert Review of Vaccines

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“…In addition, QS21 is endocytosed in a cholesterol-dependent manner and gets accumulated in lysosomes. This results in destruction of the lysosomes and releasing of lysosomal enzymes, which in turn activates the downstream immune pathways [45].…”

Section: Liposome Adjuvantsmentioning

confidence: 99%

Better Adjuvants for Better Vaccines: Progress in Adjuvant Delivery Systems, Modifications, and Adjuvant–Antigen Codelivery

Wang

2020

Vaccines

108

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Traditional aluminum adjuvants can trigger strong humoral immunity but weak cellular immunity, limiting their application in some vaccines. Currently, various immunomodulators and delivery carriers are used as adjuvants, and the mechanisms of action of some of these adjuvants are clear. However, customizing targets of adjuvant action (cellular or humoral immunity) and action intensity (enhancement or inhibition) according to different antigens selected is time-consuming. Here, we review the adjuvant effects of some delivery systems and immune stimulants. In addition, to improve the safety, effectiveness, and accessibility of adjuvants, new trends in adjuvant development and their modification strategies are discussed.

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“…QS-21 targets subcapsular macrophages in the draining lymph node and activates caspase-1 (90), potentially independently of the NLRP3-inflammasome. As a liposomal formulation QS-21 enters antigen-presenting cells by cholesterol-dependent endocytosis followed by lysosomal destabilization and activation of Syk kinase (91). It has also been proposed that this process facilitates the escape of the antigen into the cytosol, where it can enter the MHC-I pathway (92).…”

Section: Using a Recombinant Herpes Zoster Antigen With An Adjuvantmentioning

confidence: 99%

Vaccines to Prevent Infectious Diseases in the Older Population: Immunological Challenges and Future Perspectives

Wagner

Weinberger

2020

Front. Immunol.

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Infectious diseases are a major cause for morbidity and mortality in the older population. Demographic changes will lead to increasing numbers of older persons over the next decades. Prevention of infections becomes increasingly important to ensure healthy aging for the individual, and to alleviate the socioeconomic burden for societies. Undoubtedly, vaccines are the most efficient health care measure to prevent infections. Age-associated changes of the immune system are responsible for decreased immunogenicity and clinical efficacy of most currently used vaccines in older age. Efficacy of standard influenza vaccines is only 30-50% in the older population. Several approaches, such as higher antigen dose, use of MF59 as adjuvant and intradermal administration have been implemented in order to specifically target the aged immune system. The use of a 23-valent polysaccharide vaccine against Streptococcus pneumoniae has been amended by a 13-valent conjugated pneumococcal vaccine originally developed for young children several years ago to overcome at least some of the limitations of the T cell-independent polysaccharide antigens, but still is only approximately 50% protective against pneumonia. A liveattenuated vaccine against herpes zoster, which has been available for several years, demonstrated efficacy of 51% against herpes zoster and 67% against post-herpetic neuralgia. Protection was lower in the very old and decreased several years after vaccination. Recently, a recombinant vaccine containing the viral glycoprotein gE and the novel adjuvant AS01B has been licensed. Phase III studies demonstrated efficacy against herpes zoster of approx. 90% even in the oldest age groups after administration of two doses and many countries now recommend the preferential use of this vaccine. There are still many infectious diseases causing substantial morbidity in the older population, for which no vaccines are available so far. Extensive research is ongoing to develop vaccines against novel targets with several vaccine candidates already being clinically tested, which have the potential to substantially reduce health care costs and to save many lives. In addition to the development of novel and improved vaccines, which specifically target the aged immune system, it is also important to improve uptake of the existing vaccines in order to protect the vulnerable, older population.

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Lysosome-Dependent Activation of Human Dendritic Cells by the Vaccine Adjuvant QS-21

Cited by 69 publications

References 59 publications

Selection of adjuvants for vaccines targeting specific pathogens

Selection of adjuvants for vaccines targeting specific pathogens

Better Adjuvants for Better Vaccines: Progress in Adjuvant Delivery Systems, Modifications, and Adjuvant–Antigen Codelivery

Vaccines to Prevent Infectious Diseases in the Older Population: Immunological Challenges and Future Perspectives

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