Bioinformatics, Computational Informatics, and Modeling Approaches to the Design of mRNA COVID-19 Vaccine Candidates

Abstract

This article is devoted to applying bioinformatics and immunoinformatics approaches for the development of a multi-epitope mRNA vaccine against the spike glycoproteins of circulating SARS-CoV-2 variants in selected African countries. The study’s relevance is dictated by the fact that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began its global threat at the end of 2019 and since then has had a devastating impact on the whole world. Measures to reduce threats from the pandemic include social restrictions, restrictions on international travel, and vaccine development. In most cases, vaccine development depends on the spike glycoprotein, which serves as a medium for its entry into host cells. Although several variants of SARS-CoV-2 have emerged from mutations crossing continental boundaries, about 6000 delta variants have been reported along the coast of more than 20 countries in Africa, with South Africa accounting for the highest percentage. This also applies to the omicron variant of the SARS-CoV-2 virus in South Africa. The authors suggest that bioinformatics and immunoinformatics approaches be used to develop a multi-epitope mRNA vaccine against the spike glycoproteins of circulating SARS-CoV-2 variants in selected African countries. Various immunoinformatics tools have been used to predict T- and B-lymphocyte epitopes. The epitopes were further subjected to multiple evaluations to select epitopes that could elicit a sustained immunological response. The candidate vaccine consisted of seven epitopes, a highly immunogenic adjuvant, an MHC I-targeting domain (MITD), a signal peptide, and linkers. The molecular weight (MW) was predicted to be 223.1 kDa, well above the acceptable threshold of 110 kDa on an excellent vaccine candidate. In addition, the results showed that the candidate vaccine was antigenic, non-allergenic, non-toxic, thermostable, and hydrophilic. The vaccine candidate has good population coverage, with the highest range in East Africa (80.44%) followed by South Africa (77.23%). West Africa and North Africa have 76.65% and 76.13%, respectively, while Central Africa (75.64%) has minimal coverage. Among seven epitopes, no mutations were observed in 100 randomly selected SARS-CoV-2 spike glycoproteins in the study area. Evaluation of the secondary structure of the vaccine constructs revealed a stabilized structure showing 36.44% alpha-helices, 20.45% drawn filaments, and 33.38% random helices. Molecular docking of the TLR4 vaccine showed that the simulated vaccine has a high binding affinity for TLR-4, reflecting its ability to stimulate the innate and adaptive immune response.

Immunoinformatics design of a structural proteins driven multi-epitope candidate vaccine against different SARS-CoV-2 variants based on fynomer

“…This means that memory B-cells have been created. In addition, elevated levels of CTL, HTL, and IFN-γ are critical in ensuring a humoral and adaptable immune response 70 . Due to an overall improvement in the immune response to the second and third doses of the vaccine, the immune simulation has produced results consistent with the anticipated immune response.…”

Computation to Fight SARS-CoV-2 (CoVid-19)

“…The simulated vaccine exhibited a strong affinity for TLR-4, as revealed by molecular docking, indicating its capacity to activate both innate and adaptive immunity. Further in vitro and in vivo studies should be conducted after the results and performance of this computational research [20]. In an interesting paper, Singh and colleagues described a computational approach to find chemicals potentially able to recover the activity of interferon-stimulated genes (ISGs).…”

Advances of Reverse Vaccinology for mRNA Vaccine Design against SARS-CoV-2: A Review of Methods and Tools

“…By focusing on encoding only the vital epitopes in mRNA vaccines, their design becomes more efficient, which in turn improves the stability of the mRNA vaccine. In the context of COVID-19, various studies, as cited by Ahammad and Lira [27], ELKHOLY [28], Bhattacharya et al [29], Oluwagbemi et al [30], Khan et al [31], Oladipo et al [32], have advocated for a reverse vaccinology approach. This technique starts with obtaining the SARS-CoV-2 spike glycoprotein sequence, and then uses computational predictions to pinpoint epitopes for cytotoxic T lymphocytes, helper T lymphocytes, and linear B lymphocytes, while also evaluating epitope antigenicity.…”