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. 2022 Jan 17;16(6):973–984. doi: 10.1007/s11705-021-2123-1

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

Lili Yuan 1, Xiao-Dong Gao 1,, Yufei Xia 2,3,4,
PMCID: PMC8762986  PMID: 35070473

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.

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Electronic Supplementary Material

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

Keywords: pickering emulsion, vaccine adjuvant, alum-stabilised emulsion, oleic to linoleic acid ratio, stability

Electronic Supplementary Material

11705_2021_2123_MOESM1_ESM.pdf (449.1KB, pdf)

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

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).

Footnotes

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.

Contributor Information

Xiao-Dong Gao, Email: xdgao@jiangnan.edu.cn.

Yufei Xia, Email: yfxia@ipe.ac.cn.

References

  • 1.Bosch F X, Robles C, Díaz M, Arbyn M, Baussano I, Clavel C, Ronco G, Dillner J, Lehtinen M, Petry K U, et al. HPV-Faster: broadening the scope for prevention of HPV-related cancer. Nature Reviews. Clinical Oncology. 2016;13(2):119–132. doi: 10.1038/nrclinonc.2015.146. [DOI] [PubMed] [Google Scholar]
  • 2.Zhao H, Zhou X Y, Zhou Y H. Hepatitis B vaccine development and implementation. Human Vaccines & Immunotherapeutics. 2020;16(7):1533–1544. doi: 10.1080/21645515.2020.1732166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Zeng Z, Cheng L, Chen X. Progress in research on polio vaccine. Chinese Journal of Biologicals. 2019;32(6):713–716. [Google Scholar]
  • 4.Bellini C, Horvati K. Recent advances in the development of protein-and peptide-based subunit vaccines against tuberculosis. Cells. 2020;9(12):2673. doi: 10.3390/cells9122673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Cossette B, Kelly S H, Collier J H. Intranasal subunit vaccination strategies employing nanomaterials and biomaterials. ACS Biomaterials Science & Engineering. 2021;7(5):1765–1779. doi: 10.1021/acsbiomaterials.0c01291. [DOI] [PubMed] [Google Scholar]
  • 6.Do Tien D, Kim H, Jeong J, Park K H, Yang S, Oh T, Kim S, Kang I, Chae C. Comparative evaluation of the efficacy of commercial and prototype PRRS subunit vaccines against an HP-PRRSV challenge. Journal of Veterinary Medical Science. 2018;80(9):1463–1467. doi: 10.1292/jvms.17-0583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Nevagi R J, Skwarczynski M, Toth I. Polymers for subunit vaccine delivery. European Polymer Journal. 2019;114:397–410. doi: 10.1016/j.eurpolymj.2019.03.009. [DOI] [Google Scholar]
  • 8.Chao L, Xu L, Song G, Zhuang L. Emerging nanomedicine approaches fighting tumor metastasis: animal models, metastasis-targeted drug delivery, phototherapy, and immunotherapy. Chemical Society Reviews. 2016;45(22):6250–6269. doi: 10.1039/C6CS00458J. [DOI] [PubMed] [Google Scholar]
  • 9.Dupuis M, Denis-Mize K, Labarbara A, Peters W, Charo I, Mcdonald D, Ott G. Immunization with the adjuvant MF59 induces macrophage trafficking and apoptosis. European Journal of Immunology. 2015;31(10):2910–2918. doi: 10.1002/1521-4141(2001010)31:10<2910::AID-IMMU2910>3.0.CO;2-3. [DOI] [PubMed] [Google Scholar]
  • 10.Bui C, Bethmont A, Chughtai A, Gardner L, Sarkar S, Hassan S, Seale H, Macintyre C R. A systematic review of the comparative epidemiology of avian and human influenza A H5N1 and H7N9—essons and unanswered questions. Transboundary and Emerging Diseases. 2016;63(6):602–620. doi: 10.1111/tbed.12327. [DOI] [PubMed] [Google Scholar]
  • 11.Shah R R, Taccone M, Monaci E, Brito L A, Bonci A, O’Hagan D T, Amiji M M, Seubert A. The droplet size of emulsion adjuvants has significant impact on their potency, due to differences in immune cell-recruitment and-activation. Scientific Reports. 2019;9(1):11520. doi: 10.1038/s41598-019-47885-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Singh Y, Meher J G, Raval K, Khan F A, Chaurasia M, Jain N K, Chourasia M K. Nanoemulsion: concepts, development and applications in drug delivery. Journal of Controlled Release. 2017;252:28–49. doi: 10.1016/j.jconrel.2017.03.008. [DOI] [PubMed] [Google Scholar]
  • 13.Xia Y, Wu J, Du Y, Miao C, Ma G. Bridging systemic immunity with gastrointestinal immune responses via oil-in-polymer capsules. Advanced Materials. 2018;30(31):1801067. doi: 10.1002/adma.201801067. [DOI] [PubMed] [Google Scholar]
  • 14.Peng S, Cao F, Xia Y, Gao X, Dai L, Yan J, Ma G. COVID-19 vaccines: particulate alum via Pickering emulsion for an enhanced COVID-19 vaccine adjuvant. Advanced Materials. 2020;32(40):e2004210. doi: 10.1002/adma.202004210. [DOI] [PubMed] [Google Scholar]
  • 15.Song T, Xia Y, Du Y, Chen M W, Qing H, Ma G. Engineering the deformability of albumin-stabilized emulsions for lymph-node vaccine delivery. Advanced Materials. 2021;33(26):e2100106. doi: 10.1002/adma.202100106. [DOI] [PubMed] [Google Scholar]
  • 16.Xia Y, Jie W, Wei W, Du Y, Tao W, Ma X, An W, Guo A, Miao C, Hua Y. Exploiting the pliability and lateral mobility of Pickering emulsion for enhanced vaccination. Nature Materials. 2018;17(2):187–194. doi: 10.1038/nmat5057. [DOI] [PubMed] [Google Scholar]
  • 17.Shimizu N, Ito J, Kato S, Eitsuka T, Nakagawa K. Significance of squalene in rice bran oil and perspectives on aqualene oxidation. Journal of Nutritional Science and Vitaminology. 2019;65:S62–S66. doi: 10.3177/jnsv.65.S62. [DOI] [PubMed] [Google Scholar]
  • 18.Larsson K, Istenic K, Wulff T, Jonsdottir R, Kristinsson H, Freysdottir J, Undeland I, Jamnik P. Effect of in vitro digested cod liver oil of different quality on oxidative, proteomic and inflammatory responses in the yeast Saccharomyces cerevisiae and human monocyte-derived dendritic cells. Journal of the Science of Food and Agriculture. 2015;95(15):3096–3106. doi: 10.1002/jsfa.7046. [DOI] [PubMed] [Google Scholar]
  • 19.Castelli G, Bianco I D, Kiyomi Mizutamari R. Polyphenol content in argentinean commercial extra virgin olive oil. European Journal of Lipid Science and Technology. 2018;120(12):1800124. doi: 10.1002/ejlt.201800124. [DOI] [Google Scholar]
  • 20.Li Q, Tang X, Lu S, Wu J. Composition and tocopherol, fatty acid, and phytosterol contents in micro-endosperm ultra-high oil corn. Grasas y Aceites. 2019;70(3):e311. doi: 10.3989/gya.0822182. [DOI] [Google Scholar]
  • 21.Zhang T, Wang T, Liu R, Chang M, Jin Q, Wang X. Chemical characterization of fourteen kinds of novel edible oils: a comparative study using chemometrics. LWT. 2020;118:108725. doi: 10.1016/j.lwt.2019.108725. [DOI] [Google Scholar]
  • 22.Combs R, Bilyeu K. Novel alleles of FAD2-1A induce high levels of oleic acid in soybean oil. Molecular Breeding. 2019;39(6):79–90. doi: 10.1007/s11032-019-0972-9. [DOI] [Google Scholar]
  • 23.Davis J P, Price K, Dean L L, Sweigart D S, Cottonaro J, Sanders T H. Peanut oil stability and physical properties across a range of industrially relevant oleic acid/linoleic acid ratios. Peanut Science. 2016;43(1):PS14–17.1. doi: 10.3146/0095-3679-43.1.1. [DOI] [Google Scholar]
  • 24.Gnoni A, Longo S, Damiano F, Gnoni G V, Giudetti A M. Olives and Olive Oil in Health and Disease Prevention. London: Elsevier; 2021. Oleic acid and olive oil polyphenols downregulate fatty acid and cholesterol synthesis in brain and liver cells; pp. 651–657. [Google Scholar]
  • 25.Cooper J F, Weary C E, Jordan F T. The impact of non-endotoxin LAL-reactive materials on Limulus amebocyte lysate analyses. PDA Journal of Pharmaceutical Science and Technology. 1997;51(1):2–6. [PubMed] [Google Scholar]
  • 26.Symoniuk E, Ratusz K, Krygier K. Oxidative stability and the chemical composition of market cold-pressed linseed oil. European Journal of Lipid Science and Technology. 2017;119(11):1700055. doi: 10.1002/ejlt.201700055. [DOI] [Google Scholar]
  • 27.Siegler A J, Wiatrek S, Mouhanna F, Amico K R, Dominguez K, Jones J, Patel R R, Mena L A, Mayer K H. Validation of the HIV pre-exposure prophylaxis stigma scale: performance of Likert and semantic differential scale versions. AIDS and Behavior. 2020;24(9):2637–2649. doi: 10.1007/s10461-020-02820-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Fan B, Fenton O, Daly K, Ding J, Chen Q, Chen Q. Alum split applications strengthened phosphorus fixation and phosphate sorption in high legacy phosphorus calcareous soil. Journal of Enviromental Sciences. 2021;101:87–97. doi: 10.1016/j.jes.2020.08.007. [DOI] [PubMed] [Google Scholar]
  • 29.Tan H, Han L, Yang C. Effect of oil type and β-carotene incorporation on the properties of gelatin nanoparticle-stabilized pickering emulsions. LWT. 2021;141:110903. doi: 10.1016/j.lwt.2021.110903. [DOI] [Google Scholar]
  • 30.Yao X X, Liu Z, Ma M Z, Chao Y C, Gao Y X, Kong T T. Control of particle adsorption for stability of Pickering emulsions in microfluidics. Small. 2018;14(37):e1802902. doi: 10.1002/smll.201802902. [DOI] [PubMed] [Google Scholar]
  • 31.Ghimire T R, Benson R A, Garside P, Brewer J M. Alum increases antigen uptake, reduces antigen degradation and sustains antigen presentation by DCs in vitro. Immunology Letters. 2012;147(1–2):55–62. doi: 10.1016/j.imlet.2012.06.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Carrillo J, Izquierdo-Useros N, Vila-Nieto C, Pradenas E, Blanco J. Humoral immune responses and neutralizing antibodies against SARS-CoV-2: implications in pathogenesis and protective immunity. Biochemical and Biophysical Research Communications. 2021;538:187–191. doi: 10.1016/j.bbrc.2020.10.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Lin J Z, Xu R, Tian X H. Threshold dynamics of an HIV-1 model with both viral and cellular infections, cell-mediated and humoral immune responses. Mathematical Biosciences and Engineering. 2019;16(1):292–319. doi: 10.3934/mbe.2019015. [DOI] [PubMed] [Google Scholar]
  • 34.Jalkanen S, Salmi M. Lymphatic endothelial cells of the lymph node. Nature Reviews. Immunology. 2020;20(9):566–578. doi: 10.1038/s41577-020-0281-x. [DOI] [PubMed] [Google Scholar]
  • 35.Koksel Y, Gencturk M, Spano A, Reynolds M, Roshan S, Caycı Z. Utility of Likert scale (Deauville criteria) in assessment of chemoradiotherapy response of primary oropharyngeal squamous cell cancer site. Clinical Imaging. 2019;55:89–94. doi: 10.1016/j.clinimag.2019.01.007. [DOI] [PubMed] [Google Scholar]
  • 36.Krzych L J, Lach M, Joniec M, Cisowski M, Bochenek A. The Likert scale is a powerful tool for quality of life assessment among patients after minimally invasive coronary surgery. Kardiochir Torakochirurgia Pol. 2018;15(2):130–134. doi: 10.5114/kitp.2018.76480. [DOI] [PMC free article] [PubMed] [Google Scholar]

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Supplementary Materials

11705_2021_2123_MOESM1_ESM.pdf (449.1KB, pdf)

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


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