Platform for Active Vaccine Formulation Using a Two-Mode Enhancement Mechanism of Epitope Presentation by Pickering Emulsion

利用 Pickering 乳液双模式增强表位呈递机制的活性疫苗制剂平台

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作者:Guy Mechrez, Karthik Ananth Mani, Abhijit Saha, Oded Lachman, Neta Luria, Ori Molad, Liliya Kotliarevski, Einat Zelinger, Elisheva Smith, Noga Yaakov, Dalia Shabashov Stone, Meital Reches, Aviv Dombrovsky

Abstract

The efficiency of epitope-based vaccination (subunit vaccines) is tightly correlated with heterogeneity and the high density of epitope presentation, which maximizes the potential antigenic determinants. Here, we developed a two-mode platform for intensifying the epitope presentation of subunit vaccines. The two-mode epitope presentation enhancement includes a covalent attachment of high concentrations of SARS-CoV-2-S1 peptide epitope to the surface of virus-like-particles (VLPs) and the subsequent assembly of VLP/epitope conjugates on the oil droplet surface at an oil/water interface of an emulsion as Pickering stabilizers. The resultant emulsions were stable for weeks in ambient conditions, and our platform was challenged using the epitope of the SARS-CoV-2-S1 peptide that served as a model epitope in this study. In vivo assays showed that the αSARS-CoV-2-S1 immunoglobulin G (IgG) titers of the studied mouse antisera, developed against the SARS-CoV-2-S1 peptide under different epitope preparation conditions, showed an order of magnitude higher IgG titers in the studied VLP-based emulsions than epitopes dissolved in water and epitopes administered with an adjuvant, thereby confirming the efficacy of the formulation. This VLP-based Pickering emulsion platform is a fully synthetic approach that can be readily applied for vaccine development to a wide range of pathogens.

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