Design, Development and Immunogenicity Study of a Multi-Epitope Vaccine Prototype Against SARS-CoV-2

抗SARS-CoV-2多表位疫苗原型的设计、开发及免疫原性研究

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作者:Mariyana Atanasova, Ivan Dimitrov, Nikola Ralchev, Aleksandar Markovski, Iliyan Manoylov, Silviya Bradyanova, Nikolina Mihaylova, Andrey Tchorbanov, Irini Doytchinova

Conclusions

The multi-epitope vaccine prototype presented in this study demonstrates immunogenicity in mice and shows potential for human vaccine construction.

Methods

Immunoinformatic methods were used to derive models for the selection of MHC binders specific for the mouse strain used in this study among a set of human SARS-CoV-2 T cell epitopes identified in convalescent patients with COVID-19. The immunogenicity of the vaccine prototype was tested on humanized-ACE2 transgenic B6.Cg-Tg(K18-ACE2)2Prlmn/J mice by in vitro, in vivo, and ex vivo immunoassays.

Results

Eleven binders (two from the Envelope (E) protein; two from the Membrane (M) protein; three from the Spike (S) protein; and four from the Nucleocapsid (N) protein) were synthesized and included in a multi-epitope vaccine prototype. The animals were immunized with a mix of predicted MHC-I, MHC-II, or MHC-I/MHC-II peptide epitopes in Complete Freund's Adjuvant, and boosted with peptides in Incomplete Freund's Adjuvant. Immunization with SARS-CoV-2 epitopes remodeled the lymphocyte profile. A weak humoral response and the significant production of IL-4 and IFN-γ from T cells were found after the vaccination of the animals. Conclusions: The multi-epitope vaccine prototype presented in this study demonstrates immunogenicity in mice and shows potential for human vaccine construction.

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