Designing a novel mRNA vaccine against SARS-CoV-2: An immunoinformatics approach

Abstract

SARS-CoV-2 is the deadly virus behind COVID-19, the disease that went on to ravage the world and caused the biggest pandemic 21st century has witnessed so far. On the face of ongoing death and destruction, the urgent need for the discovery of a vaccine against the virus is paramount. This study resorted to the emerging discipline of immunoinformatics in order to design a multi-epitope mRNA vaccine against the spike glycoprotein of SARS-CoV-2. Various immunoinformatics tools were utilized to predict T and B lymphocyte epitopes. The epitopes were channeled through a filtering pipeline comprised of antigenicity, toxicity, allergenicity, and cytokine inducibility evaluation with the goal of selecting epitopes capable of generating both T and B cell-mediated immune responses. Molecular docking simulation between the epitopes and their corresponding MHC molecules was carried out. 13 epitopes, a highly immunogenic adjuvant, elements for proper sub-cellular trafficking, a secretion booster, and appropriate linkers were combined for constructing the vaccine. The vaccine was found to be antigenic, almost neutral at physiological pH, non-toxic, non-allergenic, capable of generating a robust immune response and had a decent worldwide population coverage. Based on these parameters, this design can be considered a promising choice for a vaccine against SARS-CoV-2.

Keywords: Immunoinformatics; SARS-CoV-2; mRNA vaccine.

Graphical abstract

Fig. 1

Workflow used for designing the mRNA vaccine against SARS-CoV-2. The whole process can be divided into two parts, pre-vaccine construction and post-vaccine construction analyses. Pre-vaccine construction analyses include the retrieval of spike glycoprotein sequence, prediction of T and B cell epitopes, population coverage prediction and molecular docking between the T cell epitopes and their MHC alleles. Post-vaccine construction analyses include the antigenicity, allergenicity, toxicity and physiochemical assessments of the vaccine construct and the simulation of immune response against the vaccine.

Fig. 2

Multiple sequence alignment of S protein sequences. The epitope sequences selected for vaccine design have been identified by boxes. None of them apparently contains any mutation.

Fig. 3

Ramachandran plots and Z score diagrams of the 3D homology models of MHC alleles. (A) HLA-A*29:02 (B) HLA-A*30:02 (C) HLA-A*32:01 (D) HLA-DRB1*04:02.

Fig. 4

Docking between the epitope VVFLHVTYV and its corresponding MHC allele, HLA-C*06:02 (A) Surface view of HLA-C*06:02 around ball and stick model of VVFLHVTYV (B) Cartoon representation of HLA-C*06:02 and ball and stick model of VVFLHVTYV.

Fig. 5

Various interactions and bond length (in angstrom) between the epitope VVFLHVTYV and the residues of its corresponding MHC allele, HLA-C*06:02 (A) Conventional hydrogen bonds (B) Hydrophobic interactions (C) Salt bridge, attractive charge interactions (D) Positive-positive repulsion (E) acceptor-acceptor clash.

Fig. 6

Population coverage of the selected T lymphocyte epitopes. Globally it covers 82.25% of the world's population. The highest and lowest areas of coverage are East Africa (87.78%) and Central America (7.16%) respectively.

Fig. 7

Proposed mechanism of synthesis, delivery and action of the mRNA vaccine against SARS-CoV-2. At first, the PCR template DNA or linearized plasmid DNA containing the designed vaccine sequences is transcribed in vitro in a media containing RNA polymerase and nucleotide phosphates. This results in a mixture of double stranded RNAs and other aberrant products. Therefore, chromatographic purification (such as FPLC) is carried out to obtain the mRNA with desired content and length. After vector-mediated delivery into the body, the mRNA transits to the cytosol. In the cytosol, the cellular translation machinery synthesizes proteins which undergo post-translational modifications, resulting in properly folded, fully functional proteins. The secretory signal and MITD sequences direct the peptides to specific compartments of the endoplasmic reticulum and Golgi body for efficient secretion (LBL) and presentation by MHC-I (HTL) and MHC-II (CTL).

Fig. 8

In silico simulation of immune response against the mRNA vaccine. (A) Immunoglobulin production in response to antigen injection (B) B cell population after three injections (C) B cell population per state (D) Helper T cell population (E) Helper T cell population per state (F) Cytotoxic T cell population per state (G) Macrophage population per state (H) Dendritic cell population per state (I) Production of cytokines and interleukins with Simpson index of the immune response.