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

2020 ◽  
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.

scholarly journals Epitope-based peptide vaccine design and target site characterization against novel coronavirus disease caused by SARS-CoV-2

2020 ◽  
Author(s):  
Lin Li ◽  
Ting Sun ◽  
Yufei He ◽  
Wendong Li ◽  
Yubo Fan ◽  
...  
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Vaccine Development ◽  
Peptide Vaccine ◽  
Human Leukocyte ◽  
Surface Glycoprotein ◽  
T Cell Epitopes ◽  
Leukocyte Antigen ◽  
The Stability ◽  
Novel Coronavirus

AbstractThe outbreak of the 2019 novel coronavirus (SARS-CoV-2) has infected thousands of people with a large number of deaths across 26 countries. The sudden appearance of the virus leads to the limited existing therapies for SARS-CoV-2. Therefore, vaccines and antiviral medicines are in desperate need. This study took immune-informatics approaches to identify B- and T-cell epitopes for surface glycoprotein (S) of SARS-CoV-2, followed by estimating their antigenicity and interactions with the human leukocyte antigen (HLA) alleles. We identified four B cell epitopes, two MHC class-I and nine MHC class-II binding T-cell epitopes, which showed highly antigenic features. Allergenicity, toxicity and physiochemical properties analysis confirmed the specificity and selectivity of epitopes. The stability and safety of epitopes were confirmed by digestion analysis. No mutations were observed in all the selected B- and T-cell epitopes across all isolates from different locations worldwide. Epitopes were thus identified and some of them can be potential candidates for vaccine development.

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

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Niti Yashvardhini ◽  
Amit Kumar ◽  
Deepak Kumar Jha
Keyword(s):  
T Cell ◽  
Rna Polymerase ◽  
B Cell ◽  
Peptide Vaccine ◽  
Human Leukocyte ◽  
World Health ◽  
T Cell Epitopes ◽  
Rna Dependent Rna Polymerase ◽  
Candidate Peptide ◽  
Antigenic Properties

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.

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

2020 ◽  
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.

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

2019 ◽  
Vol 17 (1) ◽  
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.

scholarly journals Profiling CD8+ T cell epitopes of COVID-19 convalescents reveals reduced cellular immune responses to SARS-CoV-2 variants

Cell Reports ◽  
2021 ◽  
Vol 36 (11) ◽  
pp. 109708
Author(s):  
Hang Zhang ◽  
Shasha Deng ◽  
Liting Ren ◽  
Peiyi Zheng ◽  
Xiaowen Hu ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Cd8 T Cell ◽  
T Cell Epitopes ◽  
Cellular Immune Responses ◽  
Cellular Immune

scholarly journals Immuno-informatics Design of a Multimeric Epitope Peptide Based Vaccine Targeting SARS-CoV-2 Spike Glycoprotein

2020 ◽  
Author(s):  
Onyeka S. Chukwudozie ◽  
Clive M. Gray ◽  
Tawakalt A. Fagbayi ◽  
Rebecca C. Chukwuanukwu ◽  
Victor O. Oyebanji ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
In Silico ◽  
Peptide Vaccine ◽  
Spike Protein ◽  
Cell Mediated Immunity ◽  
Epitope Peptide ◽  
Mhc I ◽  
B Cell Epitopes ◽  
Antibody Recognition

ABSTRACTDeveloping an efficacious vaccine to SARS-CoV-2 infection is critical to stem COVID-19 fatalities and providing the global community with immune protection. We have used a bioinformatic approach to aid in the design of an epitope peptide-based vaccine against the spike protein of the virus. Five antigenic B cell epitopes with viable antigenicity and a total of 27 discontinuous B cell epitopes were mapped out structurally in the spike protein for antibody recognition. We identified eight CD8+ T cell 9-mers along with 12 CD4+ T cell 14-15-mer as promising candidate epitopes putatively restricted by a large number of MHC-I and II alleles respectively. We used this information to construct an in silico chimeric peptide vaccine whose translational rate was highly expressed when cloned in pET28a (+) vector. The vaccine construct was predicted to elicit high antigenicity and cell-mediated immunity when given as a homologous prime-boost, with triggering of toll-like receptor 5 by the adjuvant linker. The vaccine was characterized by an increase in IgM and IgG and an array of Th1 and Th2 cytokines. Upon in silico challenge with SARS-CoV-2, there was a decrease in antigen levels using our immune simulations. We therefore propose that potential vaccine designs consider this approach.

scholarly journals CD171 multi‑epitope peptide design based on immunoinformatics approach as a cancer vaccine candidate for glioblastoma

2021 ◽  
Author(s):  
Seyed Amir Hossein Mohammadzadeh Hosseini Moghri ◽  
Arefeh Abbasian
Keyword(s):  
Tertiary Structure ◽  
Vaccine Development ◽  
T Cell Epitopes ◽  
Epitope Peptide ◽  
Primary Malignancy ◽  
Cellular Immune Responses ◽  
The Central Nervous System ◽  
Cellular Immune ◽  
Informatics Tools ◽  
The Brain

Abstract Glioblastoma (GB) is a common primary malignancy of the central nervous system, and one of the highly lethal brain tumors. GB cells can promote therapeutic resistance and tumor angiogenesis. The CD171 is an adhesion molecule in neuronal cells that is expressed in glioma cells; it is a regulator of the brain development. CD171 is one of the immunoglobulin-like CAMs (cell adhesion molecules) families that can be associated with prognosis in a variety of human tumors. The multi-epitope peptide vaccines are based on synthetic peptides with a combination of both B-cell epitopes and T-cell epitopes, which can induce specific humoral or cellular immune responses. In the present study, several immune-informatics tools were used for analyzing the CD171 sequence and studying the important characteristics of a designed vaccine. The results included the prediction and validation of the secondary and tertiary structure, physicochemical properties, solubility, conservancy, toxicity as well as antigenicity and allergenicity of the promising candidate for a vaccine against CD171. The immunoinformatic analysis suggested 12 predicted multi-epitope peptides, whose construction consists of 582 residues long. Therewith, cloning adaptation of designed vaccine was performed and eventually sequence was inserted into pET30a (+) vector for the application of the anti-glioblastoma vaccine development.

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

2019 ◽  
Vol 7 (8) ◽  
pp. 226 ◽  
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.

Characterization of Cellular Immune Responses to a Recombinant Idiotype Vaccine by ELISPOT and Identification of MHC Class I-Restricted T Cell Epitopes by Peptide Mapping.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1409-1409 ◽  
Author(s):  
Cristina M. Bertinetti ◽  
Hendrik Veelken
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Mhc Class I ◽  
B Cell Lymphoma ◽  
Class I ◽  
Fab Fragment ◽  
Cellular Immune Responses ◽  
Idiotype Vaccine ◽  
Cellular Immune

Abstract Induction of tumor-specific immune responses by idiotype vaccination is a promising strategy for biological therapy of indolent B cell lymphomas. In a previous report, we have described immune responses in a subset of patients participating in a phase I clinical trial primarily designed to demonstrate safety and efficacy of a recombinant idiotype vaccine (Veelken et al., ASH abstract #3342, 2003). In this trial, B-NHL patients who had relapsed after standard chemotherapy received repetitive intradermal vaccinations with recombinant idiotype Fab fragment derived from their tumor mixed with lipid-based adjuvant and concurrent subcutaneous GM-CSF at the same site. We now present the final analysis of cellular immune responses in this cohort. Peripheral blood lymphocytes (PBL) were obtained prior to and on various time points during and after vaccinations. Cryopreserved PBL were stimulated twice by autologous dendritic cells (DC) exposed to the autologous Fab protein for cross-presentation as MHC class I-bound peptides. INFγ-secreting cells were subsequently quantified by ELISPOT with Fab-presenting DC. Alternatively, freshly thawed PBL were directly assayed with recombinant Fab by ELISPOT without prestimulation. An increase in the frequency of Fab-responding PBL was detected in 7 of 15 evaluable patients with the prestimulation assay and in 4 of 10 patients by direct quantitation, resulting in a combined cellular response rate of 53% (9 of 17). A cellular immune response showed a trend for correlation with extended progression-free survival (p=0.08). T cell responses were predominantly idiotype-specific since lesser or no increases in IFNγ-secreting cells were detected against light chain- and VH family-matched control Fabs. Interestingly, a much higher base-line reactivity was observed against the control Fabs in comparison to the patient’s lymphoma Fab in four patients, pointing to the possibility of tumor-specific anergy in lymphoma patients that can at least be partially corrected by active immunization. In an effort to identify the MHC class I-presented idiotype-derived peptides, potential binding motifs were defined by reverse immunology with the SYFPEITHI algorithm (www.syfpeithi.de). Ten candidate peptides from the variable and constant region of an immune responder’s idiotype heavy chain were synthesized and evaluated with post-vaccination PBL by ELISPOT without prestimulation. A peptide derived from the CDR2 region showed a significantly higher response compared to an unrelated peptide control (p=0.0013). Additional peptides derived from the FWR1, CDR1, and CDR2 also showed a significant stimulation, but only in comparison to a no peptide control. ELISPOT offers a valuable tool to monitor cellular immune reponses and demonstrates successful induction of tumor immunity in pretreated, tumor bearing and immunosuppressed B cell lymphoma patients. Supported by Deutsche Krebshilfe

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