Computational Design of a Novel Candidate Multi-Epitope Vaccine to Boost Immune Responses against SARS‐COV‐2

2021 ◽  
Vol 18 ◽  
Author(s):  
Shiva Mohammadi ◽  
Soudabe Kavusi Pour ◽  
Mahdi Barazesh ◽  
Yadollah Bahrami ◽  
Sajad Jalili
Keyword(s):  
T Lymphocyte ◽  
Animal Studies ◽  
Cytotoxic T Lymphocyte ◽  
Cost Effective ◽  
Computational Design ◽  
Candidate Vaccine ◽  
Effective Vaccine ◽  
Epitope Vaccine ◽  
Time Saving ◽  
Binding Interface

Background: The fast development of an effective vaccine is the major demand for protection against the SARS-COV-2 virus outbreak. Immuno-informatics tools are time-saving and cost-effective methods to hasten the design and establishment of a proficient multi-peptide candidate vaccine. The utilization of multi-epitope-based vaccines has demonstrated to be a promising immunization approach against viruses due to the induction of long-term protective immunity. Method: In the present study, a complete computational approach was conducted to design a multi-epitope-based vaccine composed of cytotoxic T lymphocyte and helper T lymphocyte epitopes of Spike and Nucleocapsid proteins conserved regions. The potential viral peptides as the candidate vaccine were screened regarding convenient features like hydrophilicity, flexibility, antigenicity, and charged properties. In the next step, the vaccine efficacy needed to be improved by an immune adjuvant. For this purpose, the C-terminal domain of heat shock protein gp96 (CT-GP96) was applied as a potent adjuvant for enhancing immunity. The final assembled construct was fused with the assistance of suitable linkers and cloned in a pET28a expression vector for overproduction of the vaccine in a bacterial host. Result: Following validation of the final construct in terms of its efficacy, stability, and exposure ability, molecular docking analysis was carried out to reveal its interaction with toll-like receptor 4, which is required to trigger the immune response. The molecular simulations by iMODS software confirmed the stability of the binding interface. Additionally, the computational cloning of the assembled vaccine in pET28a plasmid showed the possibility of producing a vaccine construct post-transformation in an E. coli host. Conclusion: The computational analysis indicated that this construct could be a potent prophylactic and therapeutic multi-epitope vaccine candidate against SARS‐COV‐2 once its effectiveness is verified by experimental and animal studies.

scholarly journals Fusogenic Liposome can be Used as an Effective Vaccine Carrier for Peptide Vaccination to Induce Cytotoxic T Lymphocyte (CTL) Response

2005 ◽  
Vol 28 (1) ◽  
pp. 192-193 ◽  
Author(s):  
Toshiki Sugita ◽  
Tomoaki Yoshikawa ◽  
Jian-Qing Gao ◽  
Mariko Shimokawa ◽  
Atushi Oda ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Effective Vaccine ◽  
Peptide Vaccination ◽  
Ctl Response ◽  
Vaccine Carrier

scholarly journals Immunoinformatic based identification of cytotoxic T lymphocyte epitopes from the Indian isolate of SARS-CoV-2

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Viswajit Mulpuru ◽  
Nidhi Mishra
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Human Leukocyte ◽  
Docking Studies ◽  
Indian Isolate ◽  
Dynamics Simulation ◽  
Effective Vaccine ◽  
Ctl Epitopes ◽  
Hla System ◽  
Epitope Candidate

AbstractThe Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has turned into a pandemic with about thirty million confirmed cases worldwide as of September 2020. Being an airborne infection, it can be catastrophic to populous countries like India. This study sets to identify potential cytotoxic T lymphocyte (CTL) epitopes in the SARS-CoV-2 Indian isolate which can act as an effective vaccine epitope candidate for the majority of the Indian population. The immunogenicity and the foreignness of the epitopes towards the human body have to be studied to further confirm their candidacy. The top-scoring epitopes were subjected to molecular docking studies to study their interactions with the corresponding human leukocyte antigen (HLA) system. The CTL epitopes were observed to bind at the peptide-binding groove of the corresponding HLA system, indicating their potency as an epitope candidate. The candidacy was further analyzed using sequence conservation studies and molecular dynamics simulation. The identified epitopes can be subjected to further studies for the development of the SARS-CoV-2 vaccine.

scholarly journals Development of Multi-epitope Subunit Vaccine Against Pseudomonas aeruginosa Using OprF/OprI and PopB Proteins

2021 ◽  
Vol 16 (4) ◽  
Author(s):  
Fattaneh Sabzehali ◽  
Hossein Goudarzi ◽  
Alireza Salimi Chirani ◽  
Mohammad Hossein Yoosefi Izad ◽  
Mehdi Goudarzi
Keyword(s):  
Pseudomonas Aeruginosa ◽  
T Lymphocyte ◽  
Tertiary Structure ◽  
Vaccine Candidate ◽  
Cytotoxic T Lymphocyte ◽  
Interleukin 4 ◽  
Health Concern ◽  
Effective Vaccine ◽  
Translation Efficiency ◽  
Ligand Interaction

Background: The emerging problem of antibiotic resistance in Pseudomonas aeruginosa is a global health concern; hence, revealing innovative therapeutic approaches (such as designing an immunogenic vaccine candidate) is needed. There is no evidence of the availability of an effective vaccine that can combat the infection caused by this microorganism. Objectives: This research was conducted to develop a potential chimeric vaccine against P. aeruginosa using reverse vaccinology approaches. Methods: The present vaccine candidate comprised outer membrane protein F and I (OprF/OprI) and PopB with appropriate linkers. After applying meticulous immune-informatics investigation, the multi-epitope vaccine was created, including helper T lymphocyte (HTL), cytotoxic T lymphocyte (CTL), interferon gamma (IFN-γ), and interleukin 4 (IL-4) epitopes. Then, the physicochemical characteristics, allergenicity, toxicity, and antigenicity were analyzed. After investigating the secondary structure, the tertiary structure (3D) model was generated, refined, and validated via computational methods. Besides, the strong protein-ligand interaction and stability between the vaccine candidate and toll-like receptor 4 (TLR4) were determined via molecular docking and dynamics analyses. Moreover, in silico cloning accompanied by pET-22b (+) was used to achieve high translation efficiency. Results: Our results presumed that the chimeric-designed vaccine was thermostable and contained optimal physicochemical properties. This vaccine candidate was nontoxic and highly soluble and had stable protein and TLR4 interaction, adequately overexpressed in Escherichia coli. Overall, it could induce immune responses and repress this microorganism. Conclusions: Therefore, to inhibit Pseudomonas infections experimentally, the efficacy and safety of the vaccine design need to be validated.

scholarly journals Immunoinformatic based identification of cytotoxic T lymphocyte epitopes from the Indian isolate of SARS-CoV-2

2020 ◽  
Author(s):  
Viswajit Mulpuru ◽  
Nidhi Mishra
Keyword(s):  
T Lymphocyte ◽  
Vaccine Candidate ◽  
Cytotoxic T Lymphocyte ◽  
Human Leukocyte ◽  
Docking Studies ◽  
Indian Isolate ◽  
Effective Vaccine ◽  
Ctl Epitopes ◽  
Hla System ◽  
Peptide Binding Groove

Abstract The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has turned into a pandemic with about a million confirmed cases worldwide. Being an airborne infection, it can be highly fatal to populous countries like India. This study sets to identify potential cytotoxic T lymphocyte (CTL) epitopes in the SARS-CoV-2 Indian isolate which can acts act as an effective vaccine candidate for the majority of the Indian population. The immunogenicity and the foreignness of the epitopes towards the human body have to studies to further confirm their candidacy. The top-scoring epitopes were subjected to molecular docking studies to study their interactions with the corresponding human leukocyte antigen (HLA) system. The CTL epitopes were observed to bind at the peptide-binding groove of the corresponding HLA system, indicating their potency as a vaccine candidate. The identified epitopes can be subjected to further studies for the development of SARS-CoV-2 vaccine.

Designing of cytotoxic T lymphocyte-based multi-epitope vaccine against SARS-CoV2: a reverse vaccinology approach

2021 ◽  
pp. 1-16
Author(s):  
Reethu Vivekanandam ◽  
Kamarajan Rajagopalan ◽  
Madesh Jeevanandam ◽  
Harsha Ganesan ◽  
Vaishnavi Jagannathan ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Reverse Vaccinology ◽  
Epitope Vaccine

scholarly journals Computational Mapping of Cytotoxic T Lymphocyte epitopes of Mycobacterium Tuberculosis and their Potential Role in Vaccine Design

2021 ◽  
Author(s):  
Esakkimuthu Thangamariappan ◽  
Manikandan Mohan ◽  
Krishnan Sundar
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Lymphocyte ◽  
Potential Role ◽  
Cytotoxic T Lymphocyte ◽  
Class I ◽  
Effective Vaccine ◽  
T Cell Epitopes ◽  
Multiple Allele ◽  
Ctl Epitopes ◽  
Cell Mediated Immune Response

Objective: Tuberculosis (TB) caused by Mycobacterium tuberculosis (M. tb) is one of the deadliest diseases causing millions of deaths worldwide. Bacillus Calmette-Guérin (BCG) is the only vaccine that has been used in many countries where TB is prevalent. Despite vaccination, this disease prevails in many of the developing countries, necessitating the development of an effective vaccine against TB. Since M. tb acts as an intracellular pathogen, cell-mediated immune response plays an important role in disease control. Therefore, screening of CD8+ T cell epitopes of M. tb antigens could aid in the development of an effective vaccine against TB. In the current study, a reverse vaccinology approach was utilized to predict and map cytotoxic T lymphocyte (CTL) epitopes in the virulent proteins that are also essential for M. tb. Materials and Methods: Database of Essential Genes and Virulence Factor Database were used for identifying the virulent proteins of M. tb and their antigenicity was assessed using VaxiJen server. Various immunoinformatics tools were used to predict MHC class I binding, MHC processing, immunogenicity, toxicity and allergenicity. Results: Twelve M. tb antigens were selected for the prediction analyses using various tools. The results indicated the presence of 20 novel CTL epitopes predicted against human HLA-A alleles. This study has also screened for multiple allele binding epitopes that could be used as a vaccine component. Conclusion: This study has yielded a few hitherto unreported CTL epitopes binding to class I HLA-A alleles. Further experimental validation is necessary for confirming their potential as vaccine candidates.

scholarly journals Computationally validated SARS-CoV-2 CTL and HTL Multi-Patch Vaccines designed by reverse epitomics approach, shows potential to cover large ethnically distributed human population worldwide

2020 ◽  
Author(s):  
Sukrit Srivastava ◽  
Sonia Verma ◽  
Mohit Kamthania ◽  
Deepa Agarwal ◽  
Ajay Kumar Saxena ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Human Population ◽  
Cytotoxic T Lymphocyte ◽  
Vaccine Design ◽  
High Specificity ◽  
Effective Vaccine ◽  
Population Coverage ◽  
Hydrogen Bond Formation ◽  
Hla Alleles ◽  
Antigenic Regions

AbstractBackgroundThe SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is a positive-sense single-stranded RNA coronavirus responsible for the ongoing 2019-2020 COVID-19 outbreak. The highly contagious COVID-19 disease has spread to 216 countries in less than six months. Though several vaccine candidates are being claimed, an effective vaccine is yet to come. In present study we have designed and theoretically validated novel Multi-Patch Vaccines against SARS-CoV-2.MethodologyA novel reverse epitomics approach, “overlapping-epitope-clusters-to-patches” method is utilized to identify multiple antigenic regions from the SARS-CoV-2 proteome. These antigenic regions are here termed as “Ag-Patch or Ag-Patches”, for Antigenic Patch or Patches. The identification of Ag-Patches is based on clusters of overlapping epitopes rising from a particular region of SARS-CoV-2 protein. Further, we have utilized the identified Ag-Patches to design Multi-Patch Vaccines (MPVs), proposing a novel methodology for vaccine design and development. The designed MPVs were analyzed for immunologically crucial parameters, physiochemical properties and cDNA constructs.ResultsWe identified 73 CTL (Cytotoxic T-Lymphocyte), 49 HTL (Helper T-Lymphocyte) novel Ag-Patches from the proteome of SARS-CoV-2. The identified Ag-Patches utilized to design MPVs cover 768 (518 CTL and 250 HTL) overlapping epitopes targeting different HLA alleles. Such large number of epitope coverage is not possible for multi-epitope vaccines. The large number of epitopes covered implies large number of HLA alleles targeted, and hence large ethnically distributed human population coverage. The MPVs:Toll-Like Receptor ectodomain complex shows stable nature with numerous hydrogen bond formation and acceptable root mean square deviation and fluctuation. Further, the cDNA analysis favors high expression of the MPVs constructs in human cell line.ConclusionHighly immunogenic novel Ag-Patches are identified from the entire proteome of SARS CoV-2 by a novel reverse epitomics approach. We conclude that the novel Multi-Patch Vaccines could be a highly potential novel approach to combat SARS-CoV-2, with greater effectiveness, high specificity and large human population coverage worldwide.Abstract FigureABSTRACT FIGURE:A Multi-Patch Vaccine design to combat SARS-CoV-2 and a method to prepare thereof.Multi-Patch Vaccine designing to combat SARS-CoV-2 infection by reverse epitomics approach, “Overlapping-epitope-clusters-to-patches” method.

scholarly journals Rational Design of a Pan-Coronavirus Vaccine Based on Conserved CTL Epitopes

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 333
Author(s):  
Minchao Li ◽  
Jinfeng Zeng ◽  
Ruiting Li ◽  
Ziyu Wen ◽  
Yanhui Cai ◽  
...  
Keyword(s):  
Public Health ◽  
Genetic Algorithm ◽  
T Lymphocyte ◽  
Rational Design ◽  
Cytotoxic T Lymphocyte ◽  
Biomedical Science ◽  
Effective Vaccine ◽  
Ctl Epitopes ◽  
Global Spread ◽  
Human Coronaviruses

With the rapid global spread of the Coronavirus Disease 2019 (COVID-19) pandemic, a safe and effective vaccine against human coronaviruses (HCoVs) is believed to be a top priority in the field of public health. Due to the frequent outbreaks of different HCoVs, the development of a pan-HCoVs vaccine is of great value to biomedical science. The antigen design is a key prerequisite for vaccine efficacy, and we therefore developed a novel antigen with broad coverage based on the genetic algorithm of mosaic strategy. The designed antigen has a potentially broad coverage of conserved cytotoxic T lymphocyte (CTL) epitopes to the greatest extent, including the existing epitopes from all reported HCoV sequences (HCoV-NL63, HCoV-229E, HCoV-OC43, HCoV-HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2). This novel antigen is expected to induce strong CTL responses with broad coverage by targeting conserved epitopes against multiple coronaviruses.

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