Potential Immunogenic Activity of Computationally Designed mRNA- and Peptide-Based Prophylactic Vaccines against MERS, SARS-CoV, and SARS-CoV-2: A Reverse Vaccinology Approach

Abstract

The continued emergence of human coronaviruses (hCoVs) in the last few decades has posed an alarming situation and requires advanced cross-protective strategies against these pandemic viruses. Among these, Middle East Respiratory Syndrome coronavirus (MERS-CoV), Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), and Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) have been highly associated with lethality in humans. Despite the challenges posed by these viruses, it is imperative to develop effective antiviral therapeutics and vaccines for these human-infecting viruses. The proteomic similarity between the receptor-binding domains (RBDs) among the three viral species offers a potential target for advanced cross-protective vaccine designs. In this study, putative immunogenic epitopes including Cytotoxic T Lymphocytes (CTLs), Helper T Lymphocytes (HTLs), and Beta-cells (B-cells) were predicted for each RBD-containing region of the three highly pathogenic hCoVs. This was followed by the structural organization of peptide- and mRNA-based prophylactic vaccine designs. The validated 3D structures of these epitope-based vaccine designs were subjected to molecular docking with human TLR4. Furthermore, the CTL and HTL epitopes were processed for binding with respective human Lymphocytes Antigens (HLAs). In silico cloning designs were obtained for the prophylactic vaccine designs and may be useful in further experimental designs. Additionally, the epitope-based vaccine designs were evaluated for immunogenic activity through immune simulation. Further studies may clarify the safety and efficacy of these prophylactic vaccine designs through experimental testing against these human-pathogenic coronaviruses.

The role of SARS-CoV-2 accessory proteins in immune evasion

“… [13] . Future studies will reveal the safety and efficacy of prophylactic vaccine against coronaviruses [14] .…”

Targeted Protein-Specific Multi-Epitope-Based Vaccine Designing against Human Cytomegalovirus by Using Immunoinformatics Approaches

“…The availability of novel biological resources [ 30 , 31 ] is helpful in the design of novel therapeutics against human pathogens [ 32 , 33 ]. The shortlisting of highly antigenic target proteins and epitope sequences predicted against each protein of the HCMV were retrieved from the previously developed online resource [ 31 ], whereas the antigenic and non-antigenic proteins for each specie were identified with a VaxiJen threshold scoring system [ 34 ].…”

“…The performed allergenicity check helps to ensure the prevention of possible allergic responses in the host [ 32 ] during the vaccine designing procedures. Algpred v. 2.0 ( ; accessed on 27 September 2022) server [ 33 ] was utilized to evaluate allergenicity status of the proteins. The input sequence was added as a single letter amino acid code while the selected prediction approach was an amino acid composition based SVM module [ 33 ].…”

“…Algpred v. 2.0 ( ; accessed on 27 September 2022) server [ 33 ] was utilized to evaluate allergenicity status of the proteins. The input sequence was added as a single letter amino acid code while the selected prediction approach was an amino acid composition based SVM module [ 33 ]. The analyzed shortlisted epitopes for each target protein with potential efficacy are already available in the online resource for potential utility in vaccine construction.…”

Proteome-Wide and Protein-Specific Multi-Epitope Vaccine Constructs Against the Rift Valley Fever Virus Outbreak Using Integrated Omics Approaches

“…Furthermore, designing vaccines based on computational techniques has proven its effectiveness, specificity, safety, and stability when compared to the conventional approaches to vaccine development (Ali et al, 2019 ; Khan et al, 2019a , b , 2021a , b ; Naz et al, 2021 ). Previously, immuno-informatic strategies have been widely adopted for designing vaccines against several pathogens, including human immunodeficiency virus 1, ebola virus, herpes simplex virus 1 and 2, human norovirus, SARS-CoV, Staphylococcus aureus, Shigella spp., and Candida auris (Nosrati et al, 2019 ; Hasan et al, 2020 ; Ismail et al, 2021 ; Khan et al, 2022a , b ). Previously, several strategies have been adopted to develop vaccines against the RVF virus, which include DNA vaccines (Lagerqvist et al, 2009 ), subunit vaccines (De Boer et al, 2010 ), virus replicon particle vaccines (Kortekaas et al, 2011 ), virus-like particles (VLPs) (Mandell et al, 2010 ), modified live vaccines (Habjan et al, 2008 ), virus vectored vaccines (Warimwe et al, 2016 ), inactivated vaccines (Pittman et al, 1999 ), and live attenuated vaccines (Morrill et al, 2013 ).…”