An alternative renewable source of squalene for use in emulsion adjuvants

Brito, Luis A.; Chan, Michelle Y.; Baudner, Barbara C.; Gallorini, Simona; Santos, George França dos; O’Hagan, Derek T.; Singh, Manmohan

doi:10.1016/j.vaccine.2011.06.067

Cited by 36 publications

(24 citation statements)

References 27 publications

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“…Various emulsifier compositions exist, with squalene being the preferred metabolizable oil for vaccine adjuvant applications (1)(2)(3). Commonly used emulsifiers include Pluronics®, Tweens®, Spans®, and phospholipids.…”

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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Section: Introductionmentioning

confidence: 99%

Immunomodulatory and Physical Effects of Phospholipid Composition in Vaccine Adjuvant Emulsions

et al. 2012

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“…MF59 was studied for its ability to augment the induction of antibodies against meningococcal protein antigens [35] and the Neisseria meningitidis B vaccine [36]. The delivery of recombinant meningococcal B protein antigens in conjunction with the TLR4 agonist, E6020, within MF59 was shown to cause a strong antigen-specific CD4 T-cell response after three staged intramuscular injections into CD-1 mice [35].…”

Section: Emulsionsmentioning

confidence: 99%

Nanotechnology and vaccine development

Kim

Park

Shon

et al. 2014

Asian Journal of Pharmaceutical Sciences

119

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Emulsions Polymeric nanocarriersCarbon nanomaterials a b s t r a c t Despite the progress of conventional vaccines, improvements are clearly required due to concerns about the weak immunogenicity of these vaccines, intrinsic instability in vivo, toxicity, and the need for multiple administrations. To overcome such problems, nanotechnology platforms have recently been incorporated into vaccine development.Nanocarrier-based delivery systems offer an opportunity to enhance the humoral and cellular immune responses. This advantage is attributable to the nanoscale particle size, which facilitates uptake by phagocytic cells, the gut-associated lymphoid tissue, and the mucosa-associated lymphoid tissue, leading to efficient antigen recognition and presentation. Modifying the surfaces of nanocarriers with a variety of targeting moieties permits the delivery of antigens to specific cell surface receptors, thereby stimulating specific and selective immune responses. In this review, we introduce recent advances in nanocarrierbased vaccine delivery systems, with a focus on the types of carriers, including liposomes, emulsions, polymer-based particles, and carbon-based nanomaterials. We describe the remaining challenges and possible breakthroughs, including the development of needlefree nanotechnologies and a fundamental understanding of the in vivo behavior and stability of the nanocarriers in nanotechnology-based delivery systems.

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“…Recent work suggested that MF59 does not activate any of the Toll-like receptors in vitro but required the MyD88 adaptor protein for a Toll-like receptor-independent innate immune signaling pathway, not yet fully defined [6]. Several earlier studies revealed no bias of MF59 in generating T-helper cells of type 1 or 2 phenotype [6]. One recent study of MF59-adjuvanted H5N1 influenza vaccine demonstrated expansion of CD4 + T lymphocytes with a Th1-prone effector/memory phenotype [7].…”

Section: Mechanismmentioning

confidence: 99%

“…Not only are they effective vectors for viral transmission but they also had four-times greater rate of infection and were hospitalized more frequently than adults during the 2009/2010 H1N1 pandemic [3][4][5][6]. This was due, in part, to the fact that children had no measurable immunity to H1N1 infection prior to the pandemic [7].…”

Section: Benefits Of Adjuvanted Vaccinementioning

confidence: 99%

“…Regulatory hurdles to the approval of such added innate ligands make squalene appear to be the more straightforward path towards a simple effective adjuvant. Thus, efforts have been made with promising results using squalene from renewable sources, such as olives [6,7]; bioengineered yeast cells may also be a viable alternative for producing squalene and similar molecules. For instance, a biosynthetic isoprenoid elicited similar antibody titers to a shark-squalene emulsion when formulated with a recombinant influenza antigen and used to immunize mice (Figure 3.2).…”

Section: Emulsion Components Oilsmentioning

confidence: 99%

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