Optimising the oil phases of aluminium hydrogel-stabilised emulsions for stable, safe and efficient vaccine adjuvant

Abstract

To increase antibody secretion and dose sparing, squalene-in-water aluminium hydrogel (alum)-stabilised emulsions (ASEs) have been developed, which offer increased surface areas and cellular interactions for higher antigen loading and enhanced immune responses. Nevertheless, the squalene (oil) in previous attempts suffered from limited oxidation resistance, thus, safety and stability were compromised. From a clinical translational perspective, it is imperative to screen the optimal oils for enhanced emulsion adjuvants. Here, because of the varying oleic to linoleic acid ratio, soybean oil, peanut oil, and olive oil were utilised as oil phases in the preparation of aluminium hydrogel-stabilised squalene-in-water emulsions, which were then screened for their stability and immunogenicity. Additionally, the underlying mechanisms of oil phases and emulsion stability were unravelled, which showed that a higher oleic to linoleic acid ratio increased anti-oxidative capabilities but reduced the long-term storage stability owing to the relatively low zeta potential of the prepared droplets. As a result, compared with squalene-in-water ASEs, soybean-in-water ASEs exhibited comparable immune responses and enhanced stability. By optimising the oil phase of the emulsion adjuvants, this work may offer an alternative strategy for safe, stable, and effective emulsion adjuvants.

Graphical abstract

Keywords

pickering emulsion / vaccine adjuvant / alum-stabilised emulsion / oleic to linoleic acid ratio / stability

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Acknowledgements

This work was supported by the Project supported by Beijing Nova Program of Beijing Municipal Science & Technology Commission (Grant No. Z201100006820139), the CAS Project for Young Scientists in Basic Research (YSBR-010), the Pilot Project of Chinese Academy of Sciences (Grant No. XDB29040303), the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (Grant No. 21821005), “From 0 to 1” Original Innovation Project of Basic Frontier Scientific Research Program of Chinese Academy of Sciences (Grant No. 2020000071), Youth Project of National Natural Science Foundation of China (Grant No. 21908229), Youth Innovation Promotion Association of the Chinese Academy of Sciences (Grant No. 2020000053).

Compliance with Ethics Guidelines

All animal protocols were approved by the Institutional Animal Care and Use. Committees at the Institute of Process Engineering, Chinese Academy of Sciences (approval ID: IPEAECA20210402). This study was performed in strict accordance with the Regulations for the Care and Use of Laboratory Animals and Guideline for Ethical Review of Animal (China, GB/T35892-2018). The authors modified all the techniques and procedures to provide for maximum comfort and minimal stress to the animals.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://dx.doi.org/10.1007/s11705-021-2123-1 and is accessible for authorized users.

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