Cell death induced by vaccine adjuvants containing surfactants

Yang, Yao-Hsu; Wu, Ching-An; Morrow, W. J. W.

doi:10.1016/j.vaccine.2003.08.048

Cited by 44 publications

(45 citation statements)

References 37 publications

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“…Of interest, alum adjuvant also was reported to interact with DC membrane components to trigger DC signaling and promote CD4 + T cell activation and humoral immune responses (60). In addition, surfactants like Tweens and lipids (including liposomes, as well as saturated and unsaturated fatty acids) can differentially modulate DC-signaling cascades to augment or modify immune activation (61)(62)(63)(64)(65). Thus, membrane perturbations of DCs and other accessory cells involving lipids and surfactants may play an important role in W 80 5EC NE adjuvant activity.…”

Section: Discussionmentioning

confidence: 99%

Distinct Pathways of Humoral and Cellular Immunity Induced with the Mucosal Administration of a Nanoemulsion Adjuvant

Bielinska

Makidon

Janczak

et al. 2014

The Journal of Immunology

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Nasal administration of an oil-in-water nanoemulsion (NE) adjuvant W805EC produces potent systemic and mucosal, Th-1– and Th-17–balanced cellular responses. However, its molecular mechanism of action has not been fully characterized and is of particular interest because NE does not contain specific ligands for innate immune receptors. In these studies, we demonstrate that W805EC NE adjuvant activates innate immunity, induces specific gene transcription, and modulates NF-κB activity via TLR2 and TLR4 by a mechanism that appears to be distinct from typical TLR agonists. Nasal immunization with NE-based vaccine showed that the TLR2, TLR4, and MyD88 pathways and IL-12 and IL-12Rβ1 expression are not required for an Ab response, but they are essential for the induction of balanced Th-1 polarization and Th-17 cellular immunity. NE adjuvant induces MHC class II, CD80, and CD86 costimulatory molecule expression and dendritic cell maturation. Further, upon immunization with NE, adjuvant mice deficient in the CD86 receptor had normal Ab responses but significantly reduced Th-1 cellular responses, whereas animals deficient in both CD80 and CD86 or lacking CD40 failed to produce either humoral or cellular immunity. Overall, our data show that intranasal administration of Ag with NE induces TLR2 and TLR4 activation along with a MyD88-independent Ab response and a MyD88-dependent Th-1 and Th-17 cell–mediated immune response. These findings suggest that the unique properties of NE adjuvant may offer novel opportunities for understanding previously unrecognized mechanisms of immune activation important for generating effective mucosal and systemic immune responses.

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Section: Discussionmentioning

confidence: 99%

Distinct Pathways of Humoral and Cellular Immunity Induced with the Mucosal Administration of a Nanoemulsion Adjuvant

Bielinska

Makidon

Janczak

et al. 2014

The Journal of Immunology

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“…Non-ionic surfactants, e.g., Triton 100 and Tween 80, found in many of today's marketed vaccines, can induce apoptotic cell death [36,84], hemolysis [32,33,38], and meningoencephalitis [85]. Aluminum hydroxide gels have been used as vaccine adjuvants for many years.…”

Section: Introductionmentioning

confidence: 99%

The Initial Common Pathway of Inflammation, Disease, and Sudden Death

Davidson¹,

Seneff²

2012

Entropy

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Abstract:In reviewing the literature pertaining to interfacial water, colloidal stability, and cell membrane function, we are led to propose that a cascade of events that begins with acute exogenous surfactant-induced interfacial water stress can explain the etiology of sudden death syndrome (SDS), as well as many other diseases associated with modern times. A systemic lowering of serum zeta potential mediated by exogenous cationic surfactant administration is the common underlying pathophysiology. The cascade leads to subsequent inflammation, serum sickness, thrombohemorrhagic phenomena, colloidal instability, and ultimately even death. We propose that a sufficient precondition for sudden death is lowered bioavailability of certain endogenous sterol sulfates, sulfated glycolipids, and sulfated glycosaminoglycans, which are essential in maintaining biological equipose, energy metabolism, membrane function, and thermodynamic stability in living organisms. Our literature review provides the basis for the presentation of a novel hypothesis as to the origin of endogenous bio-sulfates which involves energy transduction from sunlight. Our hypothesis is amply supported by a growing body of data showing that parenteral administration of substances that lower serum zeta potential results in kosmotropic cationic and/or chaotropic anionic interfacial water stress, and the resulting cascade.Keywords: inflammation; serum sickness; colloidal instability; interfacial water stress; bio-sulfates; Shwartzman phenomena; sudden death syndrome Glossary of TermsAnaphylaxis a severe, rapidly progressing, life-threatening, generalized allergic reaction. Biological equipoise a stable, non-equilibrium, dissipative system synonymous with life. Cholesterol sulfate (Ch-S)quantitatively the most important known sterol sulfate in human plasma where it regulates the activity of the serine proteases, in cell membranes where it has a stabilizing role, and in platelet membranes where it supports platelet adhesion. Coherence domain (CD)a water CD is a collection of liquid water molecules which oscillate in unison in tune with a self-trapped electromagnetic field at a well-defined frequency. The coherent oscillations produce an ensemble of quasi-free electrons, able to collect noise energy from the environment and transform it into high-grade coherent energy in the form of electron vortices. This high-grade energy may then activate biomolecules resonating with the water CD. Colloidal instabilitya property attributed to a colloidal suspension that develops when stabilizing repulsive steric and electrostatic forces between colliding particles are insufficient to prevent their natural tendency to aggregate into masses large enough to precipitate.Colloidal suspension a colloid that has a continuous liquid phase in which a solid is suspended in a liquid, e.g., our flowing blood. Exclusion zone (EZ)a glass-like, gel phase consisting of water CDs resonating in-phase, adjacent to hydrophilic surfaces, several hundred micrometers wide which excludes colloi...

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“…Commonly used emulsifiers include Pluronics®, Tweens®, Spans®, and phospholipids. Emulsifier selection is based on emulsion stabilizing capacity and/or biological activity, since emulsifiers are membrane active by definition and have been shown to have various biological effects related to immune stimulation (4).…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory and Physical Effects of Phospholipid Composition in Vaccine Adjuvant Emulsions

et al. 2012

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Abstract. Egg phosphatidylcholine is commonly used as an emulsifier in formulations administered parenterally. However, synthetic phosphatidylcholine (PC) emulsifiers are now widely available and may be desirable substitutes for egg-derived phospholipids due to stability, purity, and material source considerations.In earlier work, we demonstrated that a squalene-1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) emulsion provided equivalent physical stability compared to a squalene-egg PC emulsion. In the present manuscript, we evaluate the physical stability of vaccine adjuvant emulsions containing a range of other synthetic phosphatidylcholine emulsifiers. Besides the POPC emulsion, the 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) emulsion showed good particle size and visual stability compared to emulsions made with other synthetic phospholipids. Moreover, comparable immune responses were elicited by squalene emulsions employing various synthetic PC or egg PC emulsifiers in combination with an inactivated influenza vaccine or a recombinant malaria antigen, and these responses were generally enhanced compared to antigen without adjuvant. Therefore, we show that (1) some synthetic PCs (DMPC, POPC, and to a lesser extent 1,2-dioleoyl-sn-glycero-3-phosphocholine) are effective stabilizers of squalene emulsion over a range of storage temperatures while others are not (1,2-distearoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, and 1,2-dilauroyl-sn-glycero-3-phosphocholine) and (2) the immunogenicity of stable squalene emulsions is similar regardless of PC source.

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Cell death induced by vaccine adjuvants containing surfactants

Cited by 44 publications

References 37 publications

Distinct Pathways of Humoral and Cellular Immunity Induced with the Mucosal Administration of a Nanoemulsion Adjuvant

Distinct Pathways of Humoral and Cellular Immunity Induced with the Mucosal Administration of a Nanoemulsion Adjuvant

The Initial Common Pathway of Inflammation, Disease, and Sudden Death

Immunomodulatory and Physical Effects of Phospholipid Composition in Vaccine Adjuvant Emulsions

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