PLoS ONE (Jan 2022)

Squalene in oil-based adjuvant improves the immunogenicity of SARS-CoV-2 RBD and confirms safety in animal models

  • Ricardo Choque-Guevara,
  • Astrid Poma-Acevedo,
  • Ricardo Montesinos-Millán,
  • Dora Rios-Matos,
  • Kristel Gutiérrez-Manchay,
  • Angela Montalvan-Avalos,
  • Stefany Quiñones-Garcia,
  • Maria de Grecia Cauti-Mendoza,
  • Andres Agurto-Arteaga,
  • Ingrid Ramirez-Ortiz,
  • Manuel Criollo-Orozco,
  • Edison Huaccachi-Gonzales,
  • Yomara K. Romero,
  • Norma Perez-Martinez,
  • Gisela Isasi-Rivas,
  • Yacory Sernaque-Aguilar,
  • Doris Villanueva-Pérez,
  • Freddy Ygnacio,
  • Katherine Vallejos-Sánchez,
  • Manolo Fernández-Sánchez,
  • Luis A. Guevara-Sarmiento,
  • Manolo Fernández-Díaz,
  • Mirko Zimic,
  • for the COVID-19 Working Group in Perú

Journal volume & issue
Vol. 17, no. 8

Abstract

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COVID-19 pandemic has accelerated the development of vaccines against its etiologic agent, SARS-CoV-2. However, the emergence of new variants of the virus lead to the generation of new alternatives to improve the current sub-unit vaccines in development. In the present report, the immunogenicity of the Spike RBD of SARS-CoV-2 formulated with an oil-in-water emulsion and a water-in-oil emulsion with squalene was evaluated in mice and hamsters. The RBD protein was expressed in insect cells and purified by chromatography until >95% purity. The protein was shown to have the appropriate folding as determined by ELISA and flow cytometry binding assays to its receptor, as well as by its detection by hamster immune anti-S1 sera under non-reducing conditions. In immunization assays, although the cellular immune response elicited by both adjuvants were similar, the formulation based in water-in-oil emulsion and squalene generated an earlier humoral response as determined by ELISA. Similarly, this formulation was able to stimulate neutralizing antibodies in hamsters. The vaccine candidate was shown to be safe, as demonstrated by the histopathological analysis in lungs, liver and kidney. These results have shown the potential of this formulation vaccine to be evaluated in a challenge against SARS-CoV-2 and determine its ability to confer protection.