bioRxiv (Cold Spring Harbor Laboratory) · 2020 · 35 citations · 25 references
Life SciencesImmunologyInfectious DiseasesImmunizationImmunology Of Infectious DiseasesVaccinologyAntigen DesignHuman Leukocyte Antigen SystemVaccine Antigen DesignVaccine Antigen DiscoveryViral VaccinesB-cell EpitopesCoronavirus VaccinesHla AllelesMulti-epitope Vaccine DesignMulti-epitope VaccinesPeptide EpitopesT-cell EpitopesViral Spike Proteins
Abstract A new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. An in silico approach based on the available virus genome was applied to identify 19 high immunogenic B-cell epitopes and 499 human-leukocyte-antigen (HLA) restricted T-cell epitopes. Thirty multi-epitope peptide vaccines were designed by iNeo Suite, and manufactured by solid-phase synthesis. Docking analysis showed stable hydrogen bonds of epitopes with their corresponding HLA alleles. When four vaccine peptide candidates from the spike protein of SARS-CoV-2 were selected to immunize mice, a significantly larger amount of IgG in serum as well as an increase of CD19 + cells in ILNs was observed in peptide-immunized mice compared to the control mice. The ratio of IFN-γ-secreting lymphocytes in CD4 + or CD8 + cells in the peptides-immunized mice were higher than that in the control mice. There were also a larger number of IFN-γ-secreting T cells in spleen in the peptides-immunized mice. This study screened antigenic B-cell and T-cell epitopes in all encoded proteins of SARS-CoV-2, and further designed multi-epitope based peptide vaccine against viral structural proteins. The obtained vaccine peptides successfully elicited specific humoral and cellular immune responses in mice. Primate experiments and clinical trial are urgently required to validate the efficacy and safety of these vaccine peptides. Importance So far, a new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. Different from the development approaches for traditional vaccines, the development of our peptide vaccine is faster and simpler. In this study, we performed an in silico approach to identify the antigenic B-cell epitopes and human-leukocyte-antigen (HLA) restricted T-cell epitopes, and designed a panel of multi-epitope peptide vaccines. The resulting SARS-CoV-2 multi-epitope peptide vaccine could elicit specific humoral and cellular immune responses in mice efficiently, displaying its great potential in our fight of COVID-19.
25
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
Chaolin Huang, Yeming Wang, Xingwang Li et al. · The Lancet · 2020 · 51.8K citations · Full text
SWISS-MODEL: homology modelling of protein structures and complexes
Andrew Waterhouse, Martino Bertoni, Stefan Bienert et al. · Nucleic Acids Research · 2018 · 13.6K citations · Full text
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
Daniel Wrapp, Nianshuang Wang, Kizzmekia S. Corbett et al. · Science · 2020 · 9.8K citations · Full text