A candidate multi-epitope vaccine against SARS-CoV-2

Abstract

In the past two decades, 7 coronaviruses have infected the human population, with two major outbreaks caused by SARS-CoV and MERS-CoV in the year 2002 and 2012, respectively. Currently, the entire world is facing a pandemic of another coronavirus, SARS-CoV-2, with a high fatality rate. The spike glycoprotein of SARS-CoV-2 mediates entry of virus into the host cell and is one of the most important antigenic determinants, making it a potential candidate for a vaccine. In this study, we have computationally designed a multi-epitope vaccine using spike glycoprotein of SARS-CoV-2. The overall quality of the candidate vaccine was validated in silico and Molecular Dynamics Simulation confirmed the stability of the designed vaccine. Docking studies revealed stable interactions of the vaccine with Toll-Like Receptors and MHC Receptors. The in silico cloning and codon optimization supported the proficient expression of the designed vaccine in E. coli expression system. The efficiency of the candidate vaccine to trigger an effective immune response was assessed by an in silico immune simulation. The computational analyses suggest that the designed multi-epitope vaccine is structurally stable which can induce specific immune responses and thus, can be a potential vaccine candidate against SARS-CoV-2. Wuhan, a city in China, witnessed the outbreak of a febrile respiratory illness on 19th December 2019 due to the coronavirus provisionally named as 2019-nCoV and later SARS-CoV-2 1,2. The disease caused by this coronavirus was named as COVID-19 1,2. Since then, the world is experiencing a grave situation of global public health emergency due to the viral pandemic of severe febrile pneumonia like respiratory syndrome caused by the novel coronavirus 2. Coronaviruses are known to have caused three epidemics in the last two decades, namely COVID-19 in 2019/20, Severe Acute Respiratory Syndrome (SARS) in 2002, and Middle East Respiratory Syndrome (MERS) in 2012 3. As of June 3rd 2020, total cases of SARS-CoV-2 confirmed globally by World Health Organization are 6,287,771 with 379,941 reported deaths (https ://www.who.int/emerg encie s/disea ses/ novel-coron aviru s-2019/situa tion-repor ts). Human coronavirus (H-CoV) is a member of Coronaviridae family, a virus family characterized with the largest RNA genome (26-32 kb), among all of the viruses known till date 4-6. A lipid envelope bilayer containing the spike and membrane proteins surround the positive stranded RNA genome of this virus 7. The spike protein binds to the host cell receptors and releases the viral genome into the host cell, thereby facilitating the viral replication 8. Coronaviruses (CoVs) are mostly associated with respiratory illness and common cold 9 , but can also cause infections in Central Nervous System (CNS) 10. To date, four genera of coronaviruses (α, β, γ, δ) have been identified 11. Human coronaviruses (H-CoVs) belong to α (HCoV-229E and NL63) and β (MERS-CoV, SARS-CoV, HCoV-OC43, HCoV-HKU1 and SARS-CoV-2) genera of coronavirus, respectively 11. In late De...

Multi-epitope vaccine against SARS-CoV-2 applying immunoinformatics and molecular dynamics simulation approaches

“…Recently, several groups have reported construction of multi-epitope vaccine against SARS-CoV-2 through immunoinformatics approach using various viral proteins. For instance, spike glycoprotein of SARS-CoV-2 has been evaluated extensively to design different multi-epitope vaccines (Abraham Peele et al., 2020 ; Kar et al., 2020 , Samad et al., 2020 ). Additionally, spike protein has also been used in combination of epitopes from other viral proteins including nucleocapsid and membrane (Kalita et al., 2020 ), protein 8 (Nsp8) and 3 C-like proteinase (Ahmad et al., 2020 ), main protease, Nsp12 (polymerase) and Nsp13 (helicase) (Rehman et al., 2020 ) for construction of peptide-based vaccines.…”

Unraveling the stability landscape of mutations in the SARS-CoV-2 receptor-binding domain

“…However, mutations in the spike protein and RBD of SARS-CoV and MERS-CoV are believed to have played a significant evolutionary factor in the transmission of the virus from bats to humans and influenced binding potentials to host receptors [23][24][25]. Mutations increasing affinity to virus receptors are ubiquitous [26,27], and exploring how mutations in the RBD region of SARS-CoV-2 impact the spike protein would aid in the design of better inhibitors and potential vaccines [28].…”

Peptide vaccine candidate mimics the heterogeneity of natural SARS-CoV-2 immunity in convalescent humans and induces broad T cell responses in mice models

“…In this way, it is expected that both intracellular and extracellular virus reservoirs are attacked to help rapid viral clearance, even in the absence of neutralizing antibodies. (62,63) We demonstrated that individuals' anti-SARS-CoV-2 T cell responses reactive to the PolyPEPI-SCoV-2 peptide set are HLA genotype-dependent. Specifically, multiple autologous HLA binding epitopes (PEPIs) determine antigen-specific CD8 + T cell responses with 84% accuracy.…”