Designing an efficient multi-epitope vaccine displaying interactions with diverse HLA molecules for an efficient humoral and cellular immune response to prevent COVID-19 infection

Abstract

Background: The novel SARS-CoV-2 coronavirus, the causative agent of the ongoing pandemic COVID-19 disease continues to infect people globally and has infected millions of humans worldwide. However, no effective vaccine against this virus exists. Method: Using Immunoinformatics, epitopic sequences from multiple glycoproteins that play crucial role in pathogenesis were identified. Particularly, epitopes were mapped from conserved receptorbinding domain of spike protein which have been experimentally validated in SARS-CoV-1 as a promising target for vaccine development. Results: A multi-epitopic vaccine construct comprising of B-cell, CTL, HTL epitopes was developed along with fusion of adjuvant and linkers. The epitopes identified herein are reported for the first time and were predicted to be highly antigenic, stable, nonallergen, nontoxic and displayed conservation across several SARS-CoV-2 isolates from different countries. Additionally, the epitopes associated with maximum HLA alleles and population coverage analysis shows the proposed epitopes would be a relevant representative of large proportion of the world population. A reliable three-dimensional structure of the vaccine construct was developed. Consequently, docking and molecular-dynamics simulation ensured the stable interaction between vaccine and innate-immune receptor.

Designing of a Novel Fusion Protein Vaccine Candidate Against Human Visceral Leishmaniasis (VL) Using Immunoinformatics and Structural Approaches

“…One of the crucial stages in the design and development of a vaccine candidate is the prediction of antigenic epitopes that have a potent binding affinity to different HLA alleles. So that the interaction between epitopes and MHC molecules can cause cellular immunity (Ka, Narsaria et al 2020 ; Mahapatra, Sahoo et al 2020 ). Therefore, in the current research, NetMHC 4.0 and NetMHC II servers were used to predict immunodominant MHC-I binding epitopes and MHC-II binding epitopes, respectively.…”

Next-generation computational tools and resources for coronavirus research: From detection to vaccine discovery

“…Various research organizations are working relentlessly investigating many probable vaccine candidates and technologies for SARS-CoV-2 such as the subunit vaccines, nucleic acid vaccines, and whole virus vaccines [ 104 ]. As of August 2020, 234 vaccine candidates were under development; however, none of the candidates has completed successful clinical trials to prove its efficacy and safety [ 105 ].Keeping in view the current COVID-19 situation, it is very much essential to expeditiously combine computational and experimental vaccine designing techniques to reduce the cost and time in the identification of target vaccine candidates [ 106 ], followed by further evaluation for safety and efficacy.…”

“…According to the WHO (as of August 2020), a total of146 vaccines were identified as probable candidates which are under the pre-clinical stage, 36 vaccine candidates were in clinical research(24 in Phase I–II trials, and 12 in Phase II–III trials; https://www.who.int/ ). At present, to develop a potential rapid vaccine on high priority, various computational based reports [ 106 , [134] , [135] , [136] ] have applied immunoinformatics approach to design promiscuous multi-epitope vaccine candidates using a combination of B-cell and T-cell epitopes which would provoke both cellular and humoral immune responses to successfully combat COVID-19 disease.…”

Immunoinformatic Responses of Host MHC I/II and CD4+ Cells Against Conserved Spike Fragments of SARS CoV-2 of 186 Countries With In-Silico Mutations: Implications in Universal Vaccination

“…The epitopes associated with maximum HLA alleles are the requirement of the time to ensure the viral neutralization. One report claims this outcome have been currently under trial [23]. CRISPR-mediated genome editing approach has also been used for anti-viral strategies but yet to take time to be decisive [24].…”