Exploring whole proteome to contrive multi-epitope-based vaccine for NeoCoV: An immunoinformtics and in-silico approach

Abstract

Neo-Coronavirus (NeoCoV) is a novel Betacoronavirus (β-CoVs or Beta-CoVs) discovered in bat specimens in South Africa during 2011. The viral sequence is highly similar to Middle East Respiratory Syndrome, particularly that of structural proteins. Thus, scientists have emphasized the threat posed by NeoCoV associated with human angiotensin-converting enzyme 2 (ACE2) usage, which could lead to a high death rate and faster transmission rate in humans. The development of a NeoCoV vaccine could provide a promising option for the future control of the virus in case of human infection. In silico predictions can decrease the number of experiments required, making the immunoinformatics approaches cost-effective and convenient. Herein, with the aid of immunoinformatics and reverse vaccinology, we aimed to formulate a multi-epitope vaccine that may be used to prevent and treat NeoCoV infection. Based on the NeoCoV proteins, B-cell, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) epitopes were shortlisted. Four vaccines (Neo-1–4) were devised by fusing shortlisted epitopes with appropriate adjuvants and linkers. The secondary and three-dimensional structures of final vaccines were then predicted. The binding interactions of these potential vaccines with toll-like immune receptors (TLR-2, TLR-3, and TLR-4) and major histocompatibility complex molecules (MHC-I and II) reveal that they properly fit into the receptors’ binding domains. Besides, Neo-1 and Neo-4 vaccines exhibited better docking energies of -101.08 kcal/mol and -114.47 kcal/mol, respectively, with TLR-3 as compared to other vaccine constructs. The constructed vaccines are highly antigenic, non-allergenic, soluble, non-toxic, and topologically assessable with good physiochemical characteristics. Codon optimization and in-silico cloning confirmed efficient expression of the designed vaccines in Escherichia coli strain K12. In-silico immune simulation indicated that Neo-1 and Neo-4 vaccines could induce a strong immune response against NeoCoV. Lastly, the binding stability and strong binding affinity of Neo-1 and Neo-4 with TLR-3 receptor were validated using molecular dynamics simulations and free energy calculations (Molecular Mechanics/Generalized Born Surface Area method). The final vaccines require experimental validation to establish their safety and effectiveness in preventing NeoCoV infections.

Development of multi-epitope vaccines against the monkeypox virus based on envelope proteins using immunoinformatics approaches

“…To acquire the optional vaccine candidates, five adjuvants were applied in this study. Although five selected adjuvants have been widely used in the design of multi-epitope vaccines in silico ( 48 – 51 ) and have been shown to stimulate the host’s immune response in animal experiments ( 43 , 45 , 52 – 54 ), any of these adjuvants have not been used for human vaccination. In the future, we can perform experiments to compare the immune enhancement effects of the adjuvants used in human vaccination, such as aluminum hydroxide and MF59 ( 90 ), and these adjuvants on multi-epitope vaccines.…”

“…When used as an adjuvant in certain vaccines, it is capable of resulting in stronger immune activation and higher antibody production (47). All five adjuvants have been widely used in the design of multi-epitope vaccines in silico (48)(49)(50)(51) and have been shown to stimulate the host's immune response in animal experiments (43,45,(52)(53)(54). So, in this study, each of the five adjuvants was added to the N-terminus of the vaccine using EAAAK liners, resulting in the formation of five vaccine constructs.…”

Recent advances in studying Toll-like receptors with the use of computational methods

“…The following examples are studies focused on designing vaccines against Middle East respiratory syndrome (MERS) 84 , Hepatitis C virus (HCV) 85 , human immunodeficiency virus (HIV) 86 , Neo-Coronavirus (NeoCoV) 87 , Human cytomegalovirus (HCMV) 88 , Kaposi Sarcoma 89 , as well as infections like dengue 90 , chikungunya 91 or those caused by Taenia solium 92 , Klebsiella oxytoca 93 , Klebsiella pneumoniae 94 or Mycobacterium tuberculosis 95,96 . What is also worth mentioning in the context of next-generation vaccine design is the potential use of TLR agonists as vaccine adjuvants.…”

Recent advances in studying Toll-like receptors with the use of computational methods

“…The following examples are studies focused on designing vaccines against Middle East respiratory syndrome (MERS) 85 , Hepatitis C virus (HCV) 86 , human immunodeficiency virus (HIV) 87 , Neo-Coronavirus (NeoCoV) 88 , Human cytomegalovirus (HCMV) 89 , Kaposi Sarcoma 90 , as well as infections like dengue 91 , chikungunya 92 or those caused by Taenia solium 93 , Klebsiella oxytoca 94 , Klebsiella pneumoniae 95 or Mycobacterium tuberculosis 96,97 . What is also worth mentioning in the context of next-generation vaccine design is the potential use of TLR agonists as vaccine adjuvants.…”