Stable oil-in-water emulsions: preparation and use as vaccine vehicles for lipophilic adjuvants

Woodard, L.F.; Jasman, R L

doi:10.1016/0264-410x(85)90063-5

Cited by 38 publications

(14 citation statements)

References 17 publications

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“…In the context of oil-in-water emulsion adjuvants, soybean, hexadecane, peanut, mineral, squalene, and squalane oils have been employed, although results are highly dependent on differences in emulsion preparation, antigen, and emulsifier, making comparison between different studies difficult, although squalene and especially squalane appeared to be potent substitutes for mineral oil [34-38]. Recent research using both water-in-oil and oil-in-water emulsions has examined MCT-based emulsions vs. mineral oil emulsions; the latter were more reactogenic and induced higher antibody titers [39], although the MCT-based emulsion caused a higher influx of macrophages [40].…”

Section: Discussionmentioning

confidence: 99%

“…There are at least two reports describing the effective use of one of the most common nutritional supplementation emulsions, the soybean oil-based Intralipid®, as a vaccine formulation including antigen and additional immunostimulatory molecules (muramyl dipeptide or avridine) [34, 42]. Tsujimoto et al found that the soybean emulsion with an influenza vaccine elicited similar HAI titers to the control vaccine (in PBS); however, when an additional immunostimulant (muramyl dipeptide analogue) was present, the vaccine containing the emulsion appeared to elicit higher HAI titers than the vaccine containing immunostimulant without the soybean oil emulsion [42], although the physical interaction between the immunostimulant and the emulsion was not characterized.…”

Section: Discussionmentioning

confidence: 99%

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Immunomodulatory and physical effects of oil composition in vaccine adjuvant emulsions

Fox

Baldwin

Duthie

et al. 2011

Vaccine

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Squalene-based oil-in-water emulsions have been used for years in some seasonal and pandemic influenza vaccines. However, concerns have been expressed regarding squalene source and potential biological activities. Little information is available regarding the immunomodulatory activity of squalene in comparison with other metabolizable oils in the context of oil-in-water emulsions formulated with vaccines. The present work describes the manufacture and physical characterization of emulsions composed of different classes of oils, including squalene, long chain triglycerides, a medium chain triglyceride, and a perfluorocarbon, all emulsified with egg phosphatidylcholine. Some differences were apparent among the non-squalene oils in terms of emulsion stability, including higher size polydispersity in the perfluorocarbon emulsion, more rapid visual instability at 60 °C for the long-chain triglyceride and perfluorocarbon emulsions, and an increased creaming rate in the medium-chain triglyceride emulsion at 60 °C as detected by laser scattering optical profiling. The biological activity of each of these emulsions was compared when formulated with either a recombinant malaria antigen or a split-virus inactivated influenza vaccine. Overall, vaccines containing the squalene emulsion elicited higher antibody titers and more abundant long-lived plasma cells than vaccines containing emulsions based on other oils. Since squalene-based emulsions show higher adjuvant potency compared to the other oils tested, non-squalene oils may be more suitable as carriers of amphiphilic or hydrophobic immunostimulatory molecules (such as TLR agonists) rather than as stand-alone adjuvants.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Immunomodulatory and physical effects of oil composition in vaccine adjuvant emulsions

Fox

Baldwin

Duthie

et al. 2011

Vaccine

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“…Similar results were reported on the adjuvant activity of o/w emulsions stabilized by a combination of Tween 80/Span 80 surfactants and for which the degree of stability did not affect antibody response as long as an emulsion was formed; stable emulsions were as effective as unstable ones. 32 Moreover, experiments are currently underway to examine the influence, if any, of the degree of stability of o/w liposomal emulsions on their immunogenic properties.…”

Section: Discussionmentioning

confidence: 99%

Oil-in-water liposomal emulsions: Characterization and potential use in vaccine delivery

Muderhwa¹,

Matyas²,

S̄pitler³

et al. 1999

Journal of Pharmaceutical Sciences

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Emulsification of mineral oil by phospholipids donated by liposomes composed of dimyristoyl phosphatidylcholine, dimyristoyl phosphatidylglycerol, cholesterol, and lipid A by extrusion resulted in the formation of oil-in-water liposomal emulsions containing a substantial number of intact liposomes. Increasing the proportion of liposomes from 25 mM to 150 mM phospholipid and increasing the oil content from 2.5% (v/v) to 42.5% (v/v) changed the flow characteristics of the emulsions from fluid liquid-like to viscous. Likewise, the degree of stability of the emulsions was liposomal phospholipid concentration-dependent, ranging from partial emulsification in the range 25-100 mM to complete stabilization in the range 125-150 mM. Despite some loss of liposome integrity, as evidenced by the release of liposomal trapped glucose, emulsification of liposomes containing encapsulated prostate-specific antigen (PSA) exhibited antigen-specific immunostimulation in mice. These results suggest that liposomes containing encapsulated antigen can serve as constituents for the formulation of oil-in-water vaccines.

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“…This is what Lynn Woodard [8] did at the University of Moscow (Idaho, USA) around 1980, paving the way to modern vaccine adjuvant technology. His work has been much used but was little recognized at the time.…”

Section: Woodard's Oil-in-water Emulsionsmentioning

confidence: 94%

Vaccine Adjuvants Revisited

Grubhofer¹

2008

TOVSJ

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Stable oil-in-water emulsions: preparation and use as vaccine vehicles for lipophilic adjuvants

Cited by 38 publications

References 17 publications

Immunomodulatory and physical effects of oil composition in vaccine adjuvant emulsions

Immunomodulatory and physical effects of oil composition in vaccine adjuvant emulsions

Oil-in-water liposomal emulsions: Characterization and potential use in vaccine delivery

Vaccine Adjuvants Revisited

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