tetano
Editor, Senior Moderator
Comput Biol Chem
. 2022 Aug 18;101:107754.
doi: 10.1016/j.compbiolchem.2022.107754. Online ahead of print.
Exploiting reverse vaccinology approach for the design of a multiepitope subunit vaccine against the major SARS-CoV-2 variants
Daniel Melo de Oliveira Campos[SUP] 1 [/SUP], Maria Karolaynne da Silva[SUP] 2 [/SUP], Emmanuel Duarte Barbosa[SUP] 3 [/SUP], Chiuan Yee Leow[SUP] 4 [/SUP], Umberto Laino Fulco[SUP] 5 [/SUP], Jonas Ivan Nobre Oliveira[SUP] 6 [/SUP]
Affiliations
Abstract
The current COVID-19 pandemic, an infectious disease caused by the novel coronavirus (SARS-CoV-2), poses a threat to global health because of its high rate of spread and death. Currently, vaccination is the most effective method to prevent the spread of this disease. In the present study, we developed a novel multiepitope vaccine against SARS-CoV-2 containing Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (BA.1) variants. To this end, we performed a robust immunoinformatics approach based on multiple epitopes of the four structural proteins of SARS-CoV-2 (S, M, N, and E) from 475 SARS-CoV-2 genomes sequenced from the regions with the highest number of registered cases, namely the United States, India, Brazil, France, Germany, and the United Kingdom. To investigate the best immunogenic epitopes for linear B cells, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL), we evaluated antigenicity, allergenicity, conservation, immunogenicity, toxicity, human population coverage, IFN-inducing, post-translational modifications, and physicochemical properties. The tertiary structure of a vaccine prototype was predicted, refined, and validated. Through docking experiments, we evaluated its molecular coupling to the key immune receptor Toll-Like Receptor 3 (TLR3). To improve the quality of docking calculations, quantum mechanics/molecular mechanics calculations (QM/MM) were used, with the QM part of the simulations performed using the density functional theory formalism (DFT). Cloning and codon optimization were performed for the successful expression of the vaccine in E. coli. Finally, we investigated the immunogenic properties and immune response of our SARS-CoV-2 multiepitope vaccine. The results of the simulations show that administering our prototype three times significantly increases the antibody response and decreases the amount of antigens. The proposed vaccine candidate should therefore be tested in clinical trials for its efficacy in neutralizing SARS-CoV-2.
Keywords: Immunoinformatics; Multi-epitope vaccine; Quantum mechanics/molecular mechanics calculations; SARS-CoV-2; Variants.
. 2022 Aug 18;101:107754.
doi: 10.1016/j.compbiolchem.2022.107754. Online ahead of print.
Exploiting reverse vaccinology approach for the design of a multiepitope subunit vaccine against the major SARS-CoV-2 variants
Daniel Melo de Oliveira Campos[SUP] 1 [/SUP], Maria Karolaynne da Silva[SUP] 2 [/SUP], Emmanuel Duarte Barbosa[SUP] 3 [/SUP], Chiuan Yee Leow[SUP] 4 [/SUP], Umberto Laino Fulco[SUP] 5 [/SUP], Jonas Ivan Nobre Oliveira[SUP] 6 [/SUP]
Affiliations
- PMID: 36037724
- DOI: 10.1016/j.compbiolchem.2022.107754
Abstract
The current COVID-19 pandemic, an infectious disease caused by the novel coronavirus (SARS-CoV-2), poses a threat to global health because of its high rate of spread and death. Currently, vaccination is the most effective method to prevent the spread of this disease. In the present study, we developed a novel multiepitope vaccine against SARS-CoV-2 containing Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (BA.1) variants. To this end, we performed a robust immunoinformatics approach based on multiple epitopes of the four structural proteins of SARS-CoV-2 (S, M, N, and E) from 475 SARS-CoV-2 genomes sequenced from the regions with the highest number of registered cases, namely the United States, India, Brazil, France, Germany, and the United Kingdom. To investigate the best immunogenic epitopes for linear B cells, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL), we evaluated antigenicity, allergenicity, conservation, immunogenicity, toxicity, human population coverage, IFN-inducing, post-translational modifications, and physicochemical properties. The tertiary structure of a vaccine prototype was predicted, refined, and validated. Through docking experiments, we evaluated its molecular coupling to the key immune receptor Toll-Like Receptor 3 (TLR3). To improve the quality of docking calculations, quantum mechanics/molecular mechanics calculations (QM/MM) were used, with the QM part of the simulations performed using the density functional theory formalism (DFT). Cloning and codon optimization were performed for the successful expression of the vaccine in E. coli. Finally, we investigated the immunogenic properties and immune response of our SARS-CoV-2 multiepitope vaccine. The results of the simulations show that administering our prototype three times significantly increases the antibody response and decreases the amount of antigens. The proposed vaccine candidate should therefore be tested in clinical trials for its efficacy in neutralizing SARS-CoV-2.
Keywords: Immunoinformatics; Multi-epitope vaccine; Quantum mechanics/molecular mechanics calculations; SARS-CoV-2; Variants.