Structure/function studies of QS-21 adjuvant: assessment of triterpene aldehyde and glucuronic acid roles in adjuvant function

Soltysik, Sean; Wu, Jiayan; Recchia, Joanne; Wheeler, Deborah A.; Newman, Mark J.; Coughlin, Richard T.; Kensil, Charlotte R.

doi:10.1016/0264-410x(95)00077-e

Cited by 176 publications

(121 citation statements)

References 18 publications

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“…To label QS-21, an ester derivative of QS-21 (using the glucuronic acid group) was prepared by treating QS-21 (in dimethylformamide) with sulfo-N-hydroxy succinimide and dicyclohexylcarbodiimide, as described previously (13). The QS-21-sulfo-NHS ester derivative was purified by precipitation with ethyl acetate, then dried and suspended in 0.1 M NaHPO 4 buffer (pH 7), and reacted with an excess of BODIPY FL-EDA (which bears an amine group, D2390; Life Technologies).…”

Section: Imagingmentioning

confidence: 99%

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Enhancement of Adaptive Immunity by the Human Vaccine Adjuvant AS01 Depends on Activated Dendritic Cells

Didierlaurent

Collignon

Bourguignon

et al. 2014

The Journal of Immunology

222

198

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Adjuvant System AS01 is a liposome-based vaccine adjuvant containing 3-O-desacyl-4′-monophosphoryl lipid A and the saponin QS-21. AS01 has been selected for the clinical development of several candidate vaccines including the RTS,S malaria vaccine and the subunit glycoprotein E varicella zoster vaccine (both currently in phase III). Given the known immunostimulatory properties of MPL and QS-21, the objective of this study was to describe the early immune response parameters after immunization with an AS01-adjuvanted vaccine and to identify relationships with the vaccine-specific adaptive immune response. Cytokine production and innate immune cell recruitment occurred rapidly and transiently at the muscle injection site and draining lymph node postinjection, consistent with the rapid drainage of the vaccine components to the draining lymph node. The induction of Ag-specific Ab and T cell responses was dependent on the Ag being injected at the same time or within 24 h after AS01, suggesting that the early events occurring postinjection were required for these elevated adaptive responses. In the draining lymph node, after 24 h, the numbers of activated and Ag-loaded monocytes and MHCIIhigh dendritic cells were higher after the injection of the AS01-adjuvanted vaccine than after Ag alone. However, only MHCIIhigh dendritic cells appeared efficient at and necessary for direct Ag presentation to T cells. These data suggest that the ability of AS01 to improve adaptive immune responses, as has been demonstrated in clinical trials, is linked to a transient stimulation of the innate immune system leading to the generation of high number of efficient Ag-presenting dendritic cells.

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Section: Imagingmentioning

confidence: 99%

“…2 and 11). The early evaluations of QS-21 as an adjuvant demonstrated that it could promote high Ag-specific Ab responses and CD8 + T cell responses in mice (12,13) and high Ag-specific Ab responses in humans (14). The CD8 + T cell responses induced by saponin-based vaccines presumably occurred through the promotion of Ag cross-presentation in DCs (15,16).…”

mentioning

confidence: 99%

Enhancement of Adaptive Immunity by the Human Vaccine Adjuvant AS01 Depends on Activated Dendritic Cells

Didierlaurent

Collignon

Bourguignon

et al. 2014

The Journal of Immunology

222

198

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“…O efeito hemolítico das saponinas é fortemente influenciado pela natureza polar dos substituintes ligados à aglicona (Voutquenne et al, 2002), da mesma forma que a atividade imunoadjuvante (Soltysik et al, 1995;Kensil et al, 1996), criando um universo amplo de possíveis relações estrutura-atividade. Por esse motivo, no presente trabalho foram selecionadas 20 saponinas triterpênicas pentacíclicas (Tabela 1) derivadas de ácido oleanólico, sojassapogenóis A e B, hederagenina, protoaescigenina e barringtogenol C, com as mesmas configurações em C-3, C-4, C-8, C-10, C-14, C-17 e C-20.…”

Section: Seleção Das Saponinasunclassified

“…Além disso, muitas informações relacionadas à atividade imunoadjuvante se referem especificamente às saponinas de Quillaja ou seus derivados semi-sintéticos (Soltysik et al, 1995;Kensil et al, 1996), os quais, embora apresentem uma excelente atividade imunoadjuvante, são estruturalmente diferentes de outras saponinas com atividade imunoadjuvante descrita.…”

Section: Introductionunclassified

Estudo da relação estrutura-atividade de saponinas hemolíticas e/ou imunoadjuvantes mediante uso de análise multivariada

Kaiser¹,

Pavei²,

Ortega³

2010

Rev. bras. farmacogn.

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RESUMO:Entre as diversas atividades biológicas relatadas para as saponinas, merecem destaque aquelas relacionadas ao aumento da resposta imune e a ruptura das membranas dos eritrócitos. No desenvolvimento de vacinas, ambas as propriedades exercem atividades antagônicas, contudo, as informações sobre as relações estrutura-atividade são relativamente escassas e, às vezes, conflitantes. O presente trabalho visa contribuir no estabelecimento das relações estruturais envolvidas com as atividades imunoadjuvante e hemolítica de saponinas triterpênicas. Para isso, foram selecionadas vinte saponinas de estrutura triterpênica, isoladas das espécies Aesculus hippocastanum, Dolichos lablab e Glycine max. A relação entre grupamentos substituintes do anel triterpênico e as atividades biológicas foi estudada mediante análise de agrupamentos e análise de componentes principais. Os resultados confirmam a importância da presença de açúcares em C-3 para a atividade hemolítica. Porém o efeito causado pela presença de uma hidroxila em C-16, de CH 2 OH em C-17, de uma acetila em C-22 e de um grupamento acila em C-21 sobre essa atividade parece ser mais acentuado. Já a presença de uma hidroxila em C-21, de uma metila em C-17 e de dois açúcares ligados à aglicona parece ser determinante para a atividade imunoadjuvante. Além disso, observa-se a existência de uma relação inversa entre as atividades hemolítica e imunoadjuvante.Unitermos: Saponinas, relação estrutura-atividade, atividade imunoadjuvante, atividade hemolítica, análise de agrupamentos, análise de componentes principais.ABSTRACT: "Study of the structure-activity relationship of adjuvant and/or hemolytic saponins by use of multivariate analysis". Among the various biological activities reported for saponins, those related with increase immune response and the destruction of the membrane of red blood cells deserve attention. In the development of vaccines, these properties exert antagonistic activities. However, the information about the structure-activity relationships is relatively scarce and sometimes contradictory. This paper aims to contribute to the establishment of structural relations involved with the hemolytic and adjuvant activities of triterpenic saponins by the analysis of the different groups linked to aglycone, with the use of multivariate statistical techniques. For this, we had twenty triterpenic saponins previously isolated from Aesculus hippocastanum, Dolichos lablab. and Glycine max species. Their adjuvant and hemolytic activities are available in the literature. These saponins were analyzed as groups linked to the triterpenic ring and biological activities resulting in an array of date that was submitted to cluster analysis and principal components analysis. The results confirm the importance of sugars in C-3 for hemolytic activity. However, the effect caused by the presence of a hydroxyl in C-16, CH 2 OH in C-17, acetyl in C-22 and acyl in C-21 on the hemolytic activity seems to be more important. On the other way, the presence of a hydroxyl in C-21, a meth...

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“…However, they are unable to mount a good T-cell response against soluble or exogenous antigens, a feature that is essential for the development of an effective subunit vaccine against infectious agents like Mtb. 45,46,50 Functional T cells, especially from a Th1 response, are necessary for generating a protective immune response to Mtb, 41,51 and therefore for developing an effective TB vaccine, it is essential to identify more vaccine candidates and validate these in animal models.…”

mentioning

confidence: 99%

Vaccine delivery system for tuberculosis based on nano-sized hepatitis B virus core protein particles

Dhanasooraj¹,

Kumar²,

Mundayoor³

2013

IJN

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Nano-sized hepatitis B virus core virus-like particles (HBc-VLP) are suitable for uptake by antigen-presenting cells. Mycobacterium tuberculosis antigen culture filtrate protein 10 (CFP-10) is an important vaccine candidate against tuberculosis. The purified antigen shows low immune response without adjuvant and tends to have low protective efficacy. The present study is based on the assumption that expression of these proteins on HBc nanoparticles would provide higher protection when compared to the native antigen alone. The cfp-10 gene was expressed as a fusion on the major immunodominant region of HBc-VLP, and the immune response in Balb/c mice was studied and compared to pure proteins, a mixture of antigens, and fusion protein-VLP, all without using any adjuvant. The humoral, cytokine, and splenocyte cell proliferation responses suggested that the HBc-VLP bearing CFP-10 generated an antigenspecific immune response in a Th1-dependent manner. By virtue of its self-adjuvant nature and ability to form nano-sized particles, HBc-VLPs are an excellent vaccine delivery system for use with subunit protein antigens identified in the course of recent vaccine research.

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Structure/function studies of QS-21 adjuvant: assessment of triterpene aldehyde and glucuronic acid roles in adjuvant function

Cited by 176 publications

References 18 publications

Enhancement of Adaptive Immunity by the Human Vaccine Adjuvant AS01 Depends on Activated Dendritic Cells

Enhancement of Adaptive Immunity by the Human Vaccine Adjuvant AS01 Depends on Activated Dendritic Cells

Estudo da relação estrutura-atividade de saponinas hemolíticas e/ou imunoadjuvantes mediante uso de análise multivariada

Vaccine delivery system for tuberculosis based on nano-sized hepatitis B virus core protein particles

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