Immunoinformatics Identification of B- and T-Cell Epitopes in the RNA-Dependent RNA Polymerase of SARS-CoV-2

SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) is a newly emerged beta coronavirus and etiolating agent of COVID-19. Considering the unprecedented increasing number of COVID-19 cases, the World Health Organization declared a public health emergency internationally on 11th March 2020. However, existing drugs are insufficient in dealing with this contagious virus infection; therefore, a vaccine is exigent to curb this pandemic disease. In the present study, B- and T-cell immune epitopes were identified for RdRp (RNA-dependent RNA polymerase) protein using immunoinformatic techniques, which is proved to be a rapid and efficient method to explore the candidate peptide vaccine. Subsequently, antigenicity and interactions with HLA (human leukocyte antigen) alleles were estimated. Further, physicochemical properties, allergenicity, toxicity, and stability of RdRp protein were evaluated to demonstrate the specificity of the epitope candidates. Interestingly, we identified a total of 36 B-cell and 16 T-cell epitopes using epitopes predictive tools. Among the predicted epitopes, 26 B-cell and 9 T-cell epitopes showed non-allergenic, non-toxic, and highly antigenic properties. Altogether, our study revealed that RdRp of SARS-CoV-2 (an epitope-based peptide fragment) can be a potentially good candidate for the development of a vaccine against SARS-CoV-2.

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Multi-epitope vaccine design using an immunoinformatics approach for 2019 novel coronavirus (SARS-CoV-2)

10.1101/2020.03.03.962332 ◽

2020 ◽

Cited By ~ 7

Author(s):

Ye Feng ◽

Min Qiu ◽

Liang Liu ◽

Shengmei Zou ◽

Yun Li ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Peptide Vaccine ◽

Human Leukocyte ◽

T Cell Epitopes ◽

Epitope Peptide ◽

Leukocyte Antigen ◽

Cellular Immune Responses ◽

Rapid Dissemination ◽

Cellular Immune

AbstractA new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. An in silico approach based on the available virus genome was applied to identify 19 high immunogenic B-cell epitopes and 499 human-leukocyte-antigen (HLA) restricted T-cell epitopes. Thirty multi-epitope peptide vaccines were designed by iNeo Suite, and manufactured by solid-phase synthesis. Docking analysis showed stable hydrogen bonds of epitopes with their corresponding HLA alleles. When four vaccine peptide candidates from the spike protein of SARS-CoV-2 were selected to immunize mice, a significantly larger amount of IgG in serum as well as an increase of CD19+ cells in ILNs was observed in peptide-immunized mice compared to the control mice. The ratio of IFN-γ-secreting lymphocytes in CD4+ or CD8+ cells in the peptides-immunized mice were higher than that in the control mice. There were also a larger number of IFN-γ-secreting T cells in spleen in the peptides-immunized mice. This study screened antigenic B-cell and T-cell epitopes in all encoded proteins of SARS-CoV-2, and further designed multi-epitope based peptide vaccine against viral structural proteins. The obtained vaccine peptides successfully elicited specific humoral and cellular immune responses in mice. Primate experiments and clinical trial are urgently required to validate the efficacy and safety of these vaccine peptides.ImportanceSo far, a new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. Different from the development approaches for traditional vaccines, the development of our peptide vaccine is faster and simpler. In this study, we performed an in silico approach to identify the antigenic B-cell epitopes and human-leukocyte-antigen (HLA) restricted T-cell epitopes, and designed a panel of multi-epitope peptide vaccines. The resulting SARS-CoV-2 multi-epitope peptide vaccine could elicit specific humoral and cellular immune responses in mice efficiently, displaying its great potential in our fight of COVID-19.

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In Silico Identification of Novel B Cell and T Cell Epitopes of Wuhan Coronavirus (2019-nCoV) for Effective Multi Epitope-Based Peptide Vaccine Production

10.20944/preprints202002.0359.v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Muhammad Asif Rasheed ◽

Sohail Raza ◽

Ali Zohaib ◽

Tahir Yaqub ◽

Masood Rabbani ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Vaccine Development ◽

Peptide Vaccine ◽

Surface Glycoprotein ◽

World Health ◽

Effective Vaccine ◽

Computer Assisted ◽

T Cell Epitopes ◽

Epitope Peptide

During December 2019, a novel coronavirus named as 2019-nCoV, has emerged in Wuhan, China. The human to human transmission of this virus has also been established. Untill now the virus has infected more than seven thousand people and has spread to fifteen countries. The World Health Organization (WHO) has declared 2019-nCoV as global health emergency due to its outburst well beyond China. There is need to develop some vaccines or therapeutics to control or prevent 2019-nCoV infections. The bottleneck with current conventional approaches is that these require longer time for vaccine development. However, computer assisted approaches help us to produce effective vaccine in short time compared with conventional methods. In this study, bioinformatics analysis was used to predict B cell and T cell epitopes of surface glycoprotein of 2019-nCoV that could be suitable to trigger significant immune response. The sequence of surface glycoprotein was collected from the database and analyzed to identify the immunogenic epitope. Both B cell and T cell epitopes were analyzed so the predicted epitopes can stimulate both cellular and humoral immune responses. We predicted 13 B cell and 05 T cell epitopes that later on were joined with GPGPG linker to make a single peptide. This computational approach to design a multi epitope peptide vaccine against emerging 2019-nCoV allows us to find novel immunogenic epitopes against the antigen targets of surface 2019-nCoV surface glycoprotein. This multi epitope peptide vaccine may prove effective to combat 2019-nCoV infections.

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Epitope‐based peptide vaccine design and target site depiction against Middle East Respiratory Syndrome Coronavirus: an immune-informatics study

Journal of Translational Medicine ◽

10.1186/s12967-019-2116-8 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 43

Author(s):

Muhammad Tahir ul Qamar ◽

Saman Saleem ◽

Usman Ali Ashfaq ◽

Amna Bari ◽

Farooq Anwar ◽

...

Keyword(s):

T Cell ◽

Middle East ◽

B Cell ◽

Mhc Class Ii ◽

Peptide Vaccine ◽

Middle East Respiratory Syndrome ◽

T Cell Epitopes ◽

Resistance Response ◽

B Cell Epitopes ◽

S Protein

Abstract Background Middle East Respiratory Syndrome Coronavirus (MERS-COV) is the main cause of lung and kidney infections in developing countries such as Saudi Arabia and South Korea. This infectious single-stranded, positive (+) sense RNA virus enters the host by binding to dipeptidyl-peptide receptors. Since no vaccine is yet available for MERS-COV, rapid case identification, isolation, and infection prevention strategies must be used to combat the spreading of MERS-COV infection. Additionally, there is a desperate need for vaccines and antiviral strategies. Methods The present study used immuno-informatics and computational approaches to identify conserved B- and T cell epitopes for the MERS-COV spike (S) protein that may perform a significant role in eliciting the resistance response to MERS-COV infection. Results Many conserved cytotoxic T-lymphocyte epitopes and discontinuous and linear B-cell epitopes were predicted for the MERS-COV S protein, and their antigenicity and interactions with the human leukocyte antigen (HLA) B7 allele were estimated. Among B-cell epitopes, QLQMGFGITVQYGT displayed the highest antigenicity-score, and was immensely immunogenic. Among T-cell epitopes, MHC class-I peptide YKLQPLTFL and MHC class-II peptide YCILEPRSG were identified as highly antigenic. Furthermore, docking analyses revealed that the predicted peptides engaged in strong bonding with the HLA-B7 allele. Conclusion The present study identified several MERS-COV S protein epitopes that are conserved among various isolates from different countries. The putative antigenic epitopes may prove effective as novel vaccines for eradication and combating of MERS-COV infection.

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Comparison of Neutralizing Dengue Virus B Cell Epitopes and Protective T Cell Epitopes With Those in Three Main Dengue Virus Vaccines

Frontiers in Immunology ◽

10.3389/fimmu.2021.715136 ◽

2021 ◽

Vol 12 ◽

Author(s):

Josilene Ramos Pinheiro ◽

Esther Camilo dos Reis ◽

Rayane da Silva Oliveira Souza ◽

Ana Luíza Silva Rocha ◽

Lincoln Suesdek ◽

...

Keyword(s):

T Cell ◽

Dengue Virus ◽

B Cell ◽

Public Health Problem ◽

Phase Iii ◽

World Health ◽

Human Populations ◽

T Cell Epitopes ◽

Dengue Vaccine ◽

B Cell Epitopes

The four serotypes of Dengue virus (DENV1-4) are arboviruses (arthropod-borne viruses) that belong to the Flavivirus genus, Flaviviridae family. They are the causative agents of an infectious disease called dengue, an important global public health problem with significant social-economic impact. Thus, the development of safe and effective dengue vaccines is a priority according to the World Health Organization. Only one anti-dengue vaccine has already been licensed in endemic countries and two formulations are under phase III clinical trials. In this study, we aimed to compare the main anti-dengue virus vaccines, DENGVAXIA®, LAV-TDV, and TAK-003, regarding their antigens and potential to protect. We studied the conservation of both, B and T cell epitopes involved in immunological control of DENV infection along with vaccine viruses and viral isolates. In addition, we assessed the population coverage of epitope sets contained in each vaccine formulation with regard to different human populations. As main results, we found that all three vaccines contain the main B cell epitopes involved in viral neutralization. Similarly, LAV-TDV and TAK-003 contain most of T cell epitopes involved in immunological protection, a finding not observed in DENGVAXIA®, which explains main limitations of the only licensed dengue vaccine. In summary, the levels of presence and absence of epitopes that are target for protective immune response in the three main anti-dengue virus vaccines are shown in this study. Our results suggest that investing in vaccines that contain the majority of epitopes involved in protective immunity (cellular and humoral arms) is an important issue to be considered.

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Peptide-Based Subunit Vaccine Design of T- and B-Cells Multi-Epitopes against Zika Virus Using Immunoinformatics Approaches

Microorganisms ◽

10.3390/microorganisms7080226 ◽

2019 ◽

Vol 7 (8) ◽

pp. 226 ◽

Cited By ~ 4

Author(s):

Vivitri Dewi Prasasty ◽

Karel Grazzolie ◽

Rosmalena Rosmalena ◽

Fatmawaty Yazid ◽

Fransiskus Xaverius Ivan ◽

...

Keyword(s):

B Cell ◽

Zika Virus ◽

Neutralizing Antibodies ◽

Pacific Islands ◽

Virus Disease ◽

Peptide Vaccine ◽

Human Leukocyte ◽

T Cell Epitopes ◽

B Cell Epitopes ◽

The Pacific

The Zika virus disease, also known as Zika fever is an arboviral disease that became epidemic in the Pacific Islands and had spread to 18 territories of the Americas in 2016. Zika virus disease has been linked to several health problems such as microcephaly and the Guillain–Barré syndrome, but to date, there has been no vaccine available for Zika. Problems related to the development of a vaccine include the vaccination target, which covers pregnant women and children, and the antibody dependent enhancement (ADE), which can be caused by non-neutralizing antibodies. The peptide vaccine was chosen as a focus of this study as a safer platform to develop the Zika vaccine. In this study, a collection of Zika proteomes was used to find the best candidates for T- and B-cell epitopes using the immunoinformatics approach. The most promising T-cell epitopes were mapped using the selected human leukocyte antigen (HLA) alleles, and further molecular docking and dynamics studies showed a good peptide-HLA interaction for the best major histocompatibility complex-II (MHC-II) epitope. The most promising B-cell epitopes include four linear peptides predicted to be cross-reactive with T-cells, and conformational epitopes from two proteins accessible by antibodies in their native biological assembly. It is believed that the use of immunoinformatics methods is a promising strategy against the Zika viral infection in designing an efficacious multiepitope vaccine.

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Novel epitope based peptides for vaccine against SARS-CoV-2 virus: immunoinformatics with docking approach

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20202875 ◽

2020 ◽

Vol 8 (7) ◽

pp. 2385 ◽

Cited By ~ 1

Author(s):

Jesvin Bency B. ◽

Mary Helen P. A.

Keyword(s):

B Cell ◽

Mhc Class I ◽

Mhc Class Ii ◽

Peptide Vaccine ◽

Human Leukocyte ◽

Respiratory Illness ◽

Class Ii ◽

Class I ◽

T Cell Epitopes ◽

B Cell Epitopes

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative viral strain for the contagious pandemic respiratory illness in humans which is a public health emergency of international concern. There is a desperate need for vaccines and antiviral strategies to combat the rapid spread of SARS-CoV-2 infection.Methods: The present study based on computational methods has identified novel conserved cytotoxic T-lymphocyte epitopes as well as linear and discontinuous B-cell epitopes on the SARS-CoV-2 spike (S) protein. The predicted MHC class I and class II binding peptides were further checked for their antigenic scores, allergenicity, toxicity, digesting enzymes and mutation.Results: A total of fourteen linear B-cell epitopes where GQSKRVDFC displayed the highest antigenicity-score and sixteen highly antigenic 100% conserved T-cell epitopes including the most potential vaccine candidates MHC class-I peptide KIADYNYKL and MHC class-II peptide VVFLHVTYV were identified. Furthermore, the potential peptide QGFSALEPL with high antigenicity score attached to larger number of human leukocyte antigen alleles. Docking analyses of the allele HLA-B*5201 predicted to be immunogenic to several of the selected epitopes revealed that the peptides engaged in strong binding with the HLA-B*5201 allele.Conclusions: Collectively, this research provides novel candidates for epitope-based peptide vaccine design against SARS-CoV-2 infection.

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Development of Peptide Vaccines in Dengue

Current Pharmaceutical Design ◽

10.2174/1381612823666170913163904 ◽

2018 ◽

Vol 24 (11) ◽

pp. 1157-1173 ◽

Cited By ~ 6

Author(s):

Kavita Reginald ◽

Yanqi Chan ◽

Magdalena Plebanski ◽

Chit Laa Poh

Keyword(s):

T Cell ◽

Neutralizing Antibodies ◽

Peptide Vaccine ◽

Human Leukocyte ◽

Cost Effective ◽

Cell Mediated Immunity ◽

T Cell Epitopes ◽

Peptide Vaccines ◽

Dengue Vaccine ◽

Region Data

Dengue is one of the most important arboviral infections worldwide, infecting up to 390 million people and causing 25,000 deaths annually. Although a licensed dengue vaccine is available, it is not efficacious against dengue serotypes that infect people living in South East Asia, where dengue is an endemic disease. Hence, there is an urgent need to develop an efficient dengue vaccine for this region. Data from different clinical trials indicate that a successful dengue vaccine must elicit both neutralizing antibodies and cell mediated immunity. This can be achieved by designing a multi-epitope peptide vaccine comprising B, CD8+ and CD4+ T cell epitopes. As recognition of T cell epitopes are restricted by human leukocyte antigens (HLA), T cell epitopes which are able to recognize several major HLAs will be preferentially included in the vaccine design. While peptide vaccines are safe, biocompatible and cost-effective, it is poorly immunogenic. Strategies to improve its immunogenicity by the use of long peptides, adjuvants and nanoparticle delivery mechanisms are discussed.

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Attenuated Subcomponent Vaccine Design Targeting the SARS-CoV-2 Nucleocapsid Phosphoprotein RNA Binding Domain: In Silico Analysis

Journal of Immunology Research ◽

10.1155/2020/2837670 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17

Author(s):

Onyeka S. Chukwudozie ◽

Rebecca C. Chukwuanukwu ◽

Onyekachi O. Iroanya ◽

Daniel M. Eze ◽

Vincent C. Duru ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

In Silico ◽

Rna Binding ◽

Peptide Vaccine ◽

In Silico Analysis ◽

Dynamics Simulation ◽

Effective Vaccine ◽

Translation Efficiency ◽

T Cell Epitopes

The novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has previously never been identified with humans, thereby creating devastation in public health. The need for an effective vaccine to curb this pandemic cannot be overemphasized. In view of this, we designed a subcomponent antigenic peptide vaccine targeting the N-terminal (NT) and C-terminal (CT) RNA binding domains of the nucleocapsid protein that aid in viral replication. Promising antigenic B cell and T cell epitopes were predicted using computational pipelines. The peptides “RIRGGDGKMKDL” and “AFGRRGPEQTQGNFG” were the B cell linear epitopes with good antigenic index and nonallergenic property. Two CD8+ and Three CD4+ T cell epitopes were also selected considering their safe immunogenic profiling such as allergenicity, antigen level conservancy, antigenicity, peptide toxicity, and putative restrictions to a number of MHC-I and MHC-II alleles. With these selected epitopes, a nonallergenic chimeric peptide vaccine incapable of inducing a type II hypersensitivity reaction was constructed. The molecular interaction between the Toll-like receptor-5 (TLR5) which was triggered by the vaccine was analyzed by molecular docking and scrutinized using dynamics simulation. Finally, in silico cloning was performed to ensure the expression and translation efficiency of the vaccine, utilizing the pET-28a vector. This research, therefore, provides a guide for experimental investigation and validation.

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Structure/epitope-based immunoinformatics analysis of structural proteins of 2019 novel coronavirus

10.21203/rs.3.rs-50740/v1 ◽

2020 ◽

Author(s):

Yuwei Li ◽

Mi Mao ◽

Liteng Yang ◽

Xizhuo Sun ◽

Nanshan Zhong ◽

...

Keyword(s):

T Cell ◽

Membrane Protein ◽

B Cell ◽

Envelope Protein ◽

Antiviral Treatment ◽

Peptide Vaccine ◽

Structural Proteins ◽

T Cell Epitopes ◽

B Cell Epitopes ◽

Novel Coronavirus

Abstract The newly identified 2019 novel coronavirus (2019-nCoV) has caused more than 81,400 laboratory-confirmed human infections, including 3261 deaths, posing a serious threat to human health. Currently, however, there is no specific antiviral treatment or vaccine. To identify immunodominant peptides for designing global peptide vaccine for combating the infections caused by 2019-nCoV, the structure and immunogenicity of 2019-nCoV structural protein were analyzed by bioinformatics tools. 33 B-cell epitopes and 39 T-cell epitopes were determined in four structural proteins via different immunoinformatic tools in which include spike protein (22 B-cell epitopes, 25 T-cell epitopes ), nucleocapsid protein (7 B-cell epitopes, 6 T-cell epitopes), membrane protein (2 B-cell epitopes, 7 T-cell epitopes), and envelope protein (2 B-cell epitopes, 1T-cell epitopes), respectively. The proportion of epitope residues in primary sequence was used to determine the antigenicity and immunogenicity of proteins. The envelope protein has the largest antigenicity in which residue coverage of B-cell epitopes is 24%. The membrane protein possesses the largest immunogenicity in which residue coverage of T-cell epitopes is 55.86%. The reason that immune storm was caused by 2019-nCoV maybe that the membrane and envelope protein expressed plentifully in cell infected. Further, studies involving experimental validation of these predicted epitopes is warranted to ensure the potential of B-cells and T-cells stimulation for their effective use as vaccine candidates. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection.

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Design of multi epitope-based peptide vaccine against E protein of human COVID-19: An immunoinformatics approach

10.1101/2020.02.04.934232 ◽

2020 ◽

Cited By ~ 20

Author(s):

Miyssa I. Abdelmageed ◽

Abdelrahman H. Abdelmoneim ◽

Mujahed I. Mustafa ◽

Nafisa M. Elfadol ◽

Naseem S. Murshed ◽

...

Keyword(s):

T Cell ◽

Mhc Class Ii ◽

Envelope Protein ◽

Peptide Vaccine ◽

World Health ◽

Comparative Genomic ◽

World Population ◽

T Cell Epitopes ◽

Novel Coronavirus ◽

Health Organization

AbstractBackgroundNew endemic disease has been spread across Wuhan City, China on December 2019. Within few weeks, the World Health Organization (WHO) announced a novel coronavirus designated as coronavirus disease 2019 (COVID-19). In late January 2020, WHO declared the outbreak of a “public-health emergency of international concern” due to the rapid and increasing spread of the disease worldwide. Currently, there is no vaccine or approved treatment for this emerging infection; thus the objective of this study is to design a multi epitope peptide vaccine against COVID-19 using immunoinformatics approach.MethodSeveral techniques facilitating the combination of immunoinformatics approach and comparative genomic approach were used in order to determine the potential peptides for designing the T cell epitopes-based peptide vaccine using the envelope protein of 2019-nCoV as a target.ResultsExtensive mutations, insertion and deletion were discovered with comparative sequencing in COVID-19 strain. Additionally, ten peptides binding to MHC class I and MHC class II were found to be promising candidates for vaccine design with adequate world population coverage of 88.5% and 99.99%, respectively.ConclusionT cell epitopes-based peptide vaccine was designed for COVID-19 using envelope protein as an immunogenic target. Nevertheless, the proposed vaccine is rapidly needed to be validated clinically in order to ensure its safety, immunogenic profile and to help on stopping this epidemic before it leads to devastating global outbreaks.

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