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A rational design of a multi-epitope vaccine against SARS-CoV-2 which accounts for the glycan shield of the spike glycoprotein.

ABSTRACT: The ongoing global health crisis caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus which leads to Coronavirus Disease 2019 (COVID-19) has impacted not only the health of people everywhere, but the economy in nations across the world. While vaccine candidates and therapeutics are currently undergoing clinical trials, there is a lack of proven effective treatments or cures for COVID-19. In this study, we have presented a synergistic computational platform, including molecular dynamics simulations and immunoinformatics techniques, to rationally design a multi-epitope vaccine candidate for COVID-19. This platform combines epitopes across Linear B Lymphocytes (LBL), Cytotoxic T Lymphocytes (CTL) and Helper T Lymphocytes (HTL) derived from both mutant and wild-type spike glycoproteins from SARS-CoV-2 with diverse protein conformations. In addition, this vaccine construct also takes the considerable glycan shield of the spike glycoprotein into account, which protects it from immune response. We have identified a vaccine candidate (a 35.9 kDa protein), named COVCCF, which is composed of 5 LBL, 6 HTL, and 6 CTL epitopes from the spike glycoprotein of SARS-CoV-2. Using multi-dose immune simulations, COVCCF induces elevated levels of immunoglobulin activity (IgM, IgG1, IgG2), and induces strong responses from B lymphocytes, CD4 T-helper lymphocytes, and CD8 T-cytotoxic lymphocytes. COVCCF induces cytokines important to innate immunity, including IFN-γ, IL4, and IL10. Additionally, COVCCF has ideal pharmacokinetic properties and low immune-related toxicities. In summary, this study provides a powerful, computational vaccine design platform for rapid development of vaccine candidates (including COVCCF) for effective prevention of COVID-19.Communicated by Ramaswamy H. Sarma.

SUBMITTER: Martin WR

PROVIDER: S-EPMC9003619 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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A rational design of a multi-epitope vaccine against SARS-CoV-2 which accounts for the glycan shield of the spike glycoprotein.

Martin William R WR Cheng Feixiong F

Journal of biomolecular structure & dynamics 20210310 15

The ongoing global health crisis caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus which leads to Coronavirus Disease 2019 (COVID-19) has impacted not only the health of people everywhere, but the economy in nations across the world. While vaccine candidates and therapeutics are currently undergoing clinical trials, there is a lack of proven effective treatments or cures for COVID-19. In this study, we have presented a synergistic computational platform, including ...[more]

PMID: 33715598

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Project description:Coronaviruses recently emerged as major human pathogens causing outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome. They utilize the spike (S) glycoprotein anchored in the viral envelope to mediate host attachment and fusion of the viral and cellular membranes to initiate infection. The S protein is a major determinant of the zoonotic potential of coronaviruses and is also the main target of the host humoral immune response. We report here the 3.5-Å-resolution cryo-electron microscopy structure of the S glycoprotein trimer from the pathogenic porcine deltacoronavirus (PDCoV), which belongs to the recently identified Deltacoronavirus genus. Structural and glycoproteomics data indicate that the glycans of PDCoV S are topologically conserved compared with the human respiratory coronavirus NL63 S, resulting in similar surface areas being shielded from neutralizing antibodies and implying that both viruses are under comparable immune pressure in their respective hosts. The structure further reveals a shortened S2' activation loop, containing a reduced number of basic amino acids, which participates in rendering the spike largely protease resistant. This property distinguishes PDCoV S from recently characterized betacoronavirus S proteins and suggests that the S protein of enterotropic PDCoV has evolved to tolerate the protease-rich environment of the small intestine and to fine-tune its fusion activation to avoid premature triggering and reduction of infectivity.IMPORTANCE Coronaviruses use transmembrane S glycoprotein trimers to promote host attachment and fusion of the viral and cellular membranes. We determined a near-atomic-resolution cryo-electron microscopy structure of the S ectodomain trimer from the pathogenic PDCoV, which is responsible for diarrhea in piglets and has had devastating consequences for the swine industry worldwide. Structural and glycoproteomics data reveal that PDCoV S is decorated with 78 N-linked glycans obstructing the protein surface to limit accessibility to neutralizing antibodies in a way reminiscent of what has recently been described for a human respiratory coronavirus. PDCoV S is largely protease resistant, which distinguishes it from most other characterized coronavirus S glycoproteins and suggests that enteric coronaviruses have evolved to fine-tune fusion activation in the protease-rich environment of the small intestine of infected hosts.

Dataset Information

A rational design of a multi-epitope vaccine against SARS-CoV-2 which accounts for the glycan shield of the spike glycoprotein.

Publications

A rational design of a multi-epitope vaccine against SARS-CoV-2 which accounts for the glycan shield of the spike glycoprotein.

Similar Datasets

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