The droplet size of emulsion adjuvants has significant impact on their potency, due to differences in immune cell-recruitment and -activation

Shah, R. Y.; Taccone, Marianna; Monaci, Elisabetta; Brito, Luis A.; Bonci, Alessandra; O’Hagan, Derek T.; Amiji, Mansoor M.; Seubert, Anja

doi:10.1038/s41598-019-47885-z

Cited by 29 publications

(33 citation statements)

References 15 publications

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“…The results demonstrate the ability of Synthetic Biology-derived triterpene oils, of high purity and of nonanimal origin, to perform statistically as well in an O/W adjuvant formulation when compared to the current source of squalene using standard immunological markers for this type of adjuvant/vaccine study (i.e. IgG1, IgG2a, total IgG, and HI titers) 23,[43][44][45] . In both physiochemical and immunogenic properties, the Synthetic Biology produced squalene, botryococcene and methylated squalene performed equivalent to shark-derived squalene based on immunological activity.…”

Section: Discussionmentioning

confidence: 76%

Synthetic Biology-derived triterpenes as efficacious immunomodulating adjuvants

Tateno

Stone

Srodulski

et al. 2020

Sci Rep

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The triterpene oil squalene is an essential component of nanoemulsion vaccine adjuvants. It is most notably in the MF59 adjuvant, a component in some seasonal influenza vaccines, in stockpiled, emulsion-based adjuvanted pandemic influenza vaccines, and with demonstrated efficacy for vaccines to other pandemic viruses, such as SARS-CoV-2. Squalene has historically been harvested from shark liver oil, which is undesirable for a variety of reasons. In this study, we have demonstrated the use of a Synthetic Biology (yeast) production platform to generate squalene and novel triterpene oils, all of which are equally as efficacious as vaccine adjuvants based on physiochemical properties and immunomodulating activities in a mouse model. These Synthetic Biology adjuvants also elicited similar IgG1, IgG2a, and total IgG levels compared to marine and commercial controls when formulated with common quadrivalent influenza antigens. Injection site morphology and serum cytokine levels did not suggest any reactogenic effects of the yeast-derived squalene or novel triterpenes, suggesting their safety in adjuvant formulations. These results support the advantages of yeast produced triterpene oils to include completely controlled growth conditions, just-in-time and scalable production, and the capacity to produce novel triterpenes beyond squalene.

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Section: Discussionmentioning

confidence: 76%

Synthetic Biology-derived triterpenes as efficacious immunomodulating adjuvants

Tateno

Stone

Srodulski

et al. 2020

Sci Rep

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“…The exact mode of action of alum is still investigated and includes multiple pathways [ 35 ]: the presentation of the antigen on an alum particle improves the interaction with APCs; alum itself can interact with lipids on APCs membrane, activating the cells, and alum activates inflammasome, resulting into activation of innate immunity. Alternatively, oil-in-water emulsions (e.g., MF59) do not directly interact with APCs but modify the immune contexture surrounding the administration spot facilitating the migration of APCs [ 36 ]. The size of the emulsion droplet is of the utmost importance for the efficacy of the vaccination; too small particles have lower efficacy than 160 nm droplets [ 36 ].…”

Section: Past: Conventional Vaccine Formulationsmentioning

confidence: 99%

Development of vaccine formulations: past, present, and future

D'Amico

Fontana

Chen

et al. 2021

Drug Deliv. and Transl. Res.

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The current situation, heavily influenced by the ongoing pandemic, puts vaccines back into the spotlight. However, the conventional and traditional vaccines present disadvantages, particularly related to immunogenicity, stability, and storage of the final product. Often, such products require the maintenance of a “cold chain,” impacting the costs, the availability, and the distribution of vaccines. Here, after a recall of the mode of action of vaccines and the types of vaccines currently available, we analyze the past, present, and future of vaccine formulation. The past focuses on conventional formulations, the present discusses the use of nanoparticles for vaccine delivery and as adjuvants, while the future presents microneedle patches as alternative formulation and administration route. Finally, we compare the advantages and disadvantages of injectable solutions, nanovaccines, and microneedles in terms of efficacy, stability, and patient-friendly design. Graphical abstract Different approaches to vaccine formulation development, the conventional vaccine formulations from the past, the current development of lipid nanoparticles as vaccines, and the near future microneedles formulations are discussed in this review.

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“…Contrastingly, nanoemulsions with smaller droplet size are inferior adjuvants, but with better safety profile (64). In the study of Shah et al (66) it was highlighted that there was no benefit in reducing nanoemulsion droplet size below 160 nm -both for humoral and cellular immune response. Taken all together -efficacy and safety profile of nanoemulsion-based adjuvants, their stability and possibility to undergo sterile filtration, it may be concluded that "smaller is not always the better".…”

Section: Physicochemical Properties Of Nanoemulsion-based Adjuvantsmentioning

confidence: 99%

Established and advanced adjuvants in vaccines' formulation: Mineral adsorbents, nanoparticulate carriers and microneedle delivery systems

Krajišnik¹,

Ilić²,

Nikolić³

et al. 2019

Arhiv za farmaciju

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In the era of modern vaccinology, limited immunogenicity of the most commonly used antigens has enforced the use of various adjuvants in vaccine formulations to achieve desired immune response. Aluminum-containing adjuvants have been, historically, the most widely used mineral immunostimulants, generally regarded as safe to use in human vaccines. The great academic progress in inorganic (nano)materials synthesis, structure control and functionalization design has led to a growing interest in innovative adjuvants such as clays, mesoporous silica nanoparticles, zinc oxide, iron oxide and iron hydroxide nanoparticles, etc. On the other hand, there has been an intention to use specific nanoparticulated antigen delivery systems, such as nanoemulsions, in order to protect antigens from premature proteolytic degradation and/or to improve antigen immunogenicity by facilitating antigen uptake and processing by antigen presenting cells. Simultaneously, numerous research efforts have been focused on the development of innovative technologies for antigen delivery into the skin (such as microneedles), with the aim to improve vaccine efficacy alongside with enhanced patient adherence, particularly in children population (noninvasive or minimally invasive administration). Therefore, this review deals with each of these approaches in more detail, with the special emphasis on examples of their use in vaccine formulations as well as on the factors influencing their efficacy and safety.

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The droplet size of emulsion adjuvants has significant impact on their potency, due to differences in immune cell-recruitment and -activation

Cited by 29 publications

References 15 publications

Synthetic Biology-derived triterpenes as efficacious immunomodulating adjuvants

Synthetic Biology-derived triterpenes as efficacious immunomodulating adjuvants

Development of vaccine formulations: past, present, and future

Established and advanced adjuvants in vaccines' formulation: Mineral adsorbents, nanoparticulate carriers and microneedle delivery systems

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