scholarly journals Design of an epitope-based peptide vaccine against the SARS-CoV-2: a vaccine-informatics approach

2020 ◽  
Author(s):  
Aftab Alam ◽  
Arbaaz Khan ◽  
Nikhat Imam ◽  
Mohd Faizan Siddiqui ◽  
Mohd Waseem ◽  
...  
Keyword(s):  
T Cell ◽  
Vaccine Development ◽  
Peptide Vaccine ◽  
Specific Treatment ◽  
T Cell Response ◽  
Surface Glycoprotein ◽  
Antigenic Peptides ◽  
Population Coverage ◽  
Geographical Regions ◽  
Cluster Of Differentiation

Abstract The recurrent and recent global outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has turned into a global concern which has infected more than 42 million people all over the globe, and this number is increasing in hours. Unfortunately, no vaccine or specific treatment is available, which makes it more deadly. A vaccine-informatics approach has shown significant breakthrough in peptide-based epitope mapping and opens the new horizon in vaccine development. In this study, we have identified a total of 15 antigenic peptides [including thymus cells (T-cells) and bone marrow or bursa-derived cells] in the surface glycoprotein (SG) of SARS-CoV-2 which is nontoxic and nonallergenic in nature, nonallergenic, highly antigenic and non-mutated in other SARS-CoV-2 virus strains. The population coverage analysis has found that cluster of differentiation 4 (CD4+) T-cell peptides showed higher cumulative population coverage over cluster of differentiation 8 (CD8+) peptides in the 16 different geographical regions of the world. We identified 12 peptides ((LTDEMIAQY, WTAGAAAYY, WMESEFRVY, IRASANLAA, FGAISSVLN, VKQLSSNFG, FAMQMAYRF, FGAGAALQI, YGFQPTNGVGYQ, LPDPSKPSKR, QTQTNSPRRARS and VITPGTNTSN) that are $80\hbox{--} 90\%$ identical with experimentally determined epitopes of SARS-CoV, and this will likely be beneficial for a quick progression of the vaccine design. Moreover, docking analysis suggested that the identified peptides are tightly bound in the groove of human leukocyte antigen molecules which can induce the T-cell response. Overall, this study allows us to determine potent peptide antigen targets in the SG on intuitive grounds, which opens up a new horizon in the coronavirus disease (COVID-19) research. However, this study needs experimental validation by in vitro and in vivo.

scholarly journals Design of an Epitope-Based Peptide Vaccine against the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): A Vaccine-informatics Approach

2020 ◽  
Author(s):  
Aftab Alam ◽  
Arbaaz Khan ◽  
Nikhat Imam ◽  
Mohd Faizan Siddiqui ◽  
Mohd Waseem ◽  
...  
Keyword(s):  
T Cell ◽  
Vaccine Development ◽  
Peptide Vaccine ◽  
Specific Treatment ◽  
T Cell Response ◽  
Surface Glycoprotein ◽  
Antigenic Peptides ◽  
Population Coverage ◽  
Geographical Regions

AbstractThe recurrent and recent global outbreak of SARS-CoV-2 has turned into a global concern which has infected more than 19-million people all over the globe, and this number is increasing in hours. Unfortunate no vaccine or specific treatment is available, which make it more deadly. A vaccine-informatics approach has shown significant breakthrough in peptide-based epitope mapping and opens the new horizon in vaccine development. In this study, we have identified a total of 15 antigenic peptides (including T and B cells) in the surface glycoprotein of SARS-CoV-2 which showed non-toxic nature, non-allergenic, highly antigenic and non-mutated in other SARS-CoV-2 virus strains. The population coverage analysis has found that CD4+ T-cell peptides showed higher cumulative population coverage over to CD8+ peptides in the 16 different geographical regions of the world. We identified twelve peptides (LTDEMIAQY, WTAGAAAYY, WMESEFRVY, IRASANLAA, FGAISSVLN, VKQLSSNFG, FAMQMAYRF, FGAGAALQI, YGFQPTNGVGYQ, LPDPSKPSKR, QTQTNSPRRARS and VITPGTNTSN) that are 80% - 90% identical with experimentally determined epitopes of SARS-CoV, and this will likely be beneficial for a quick progression of the vaccine design. Moreover, docking analysis suggested that identified peptides are tightly bound in the groove of HLA molecules which can induce the T-cell response. Overall this study allows us to determine potent peptide antigen targets in surface glycoprotein on intuitive grounds which open up a new horizon in COVID-19 research. However, this study needs experimental validation by in vitro and in vivo.

scholarly journals Design of Peptide Vaccine for COVID19: CD8+ and CD4+ T cell epitopes from SARS-CoV-2 open-reading-frame protein variants

2021 ◽  
Author(s):  
Simone Parn ◽  
Gabriel Jabbour ◽  
Vincent Nguyenkhoa ◽  
Sivanesan Dakshanamurthy
Keyword(s):  
T Cell ◽  
Vaccine Development ◽  
Human Life ◽  
Peptide Vaccine ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
World Population ◽  
T Cell Epitopes ◽  
The World ◽  
Potential Vaccine

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has challenged public health at an unprecedented scale which has led to a dramatic loss of human life worldwide. To design a protective vaccine against SARS-CoV-2, it is necessary to understand which SARS-CoV-2 specific epitopes can elicit a T cell response and provide protection across a broad population. In this study, PLpro and RdRp, two immunogenic non-structural proteins from an immunodominant gene region ORF1ab, as well as ORF3a and ORF9b are identified as potential vaccine targets against SARS-CoV-2. To select top epitopes for vaccine design, we used various clinical properties, such as antigenicity, allergenicity, toxicity and IFN-y secretion. The analysis of CD8 and CD4 T cell epitopes revealed multiple potential vaccine constructs that cover a high percentage of the world population. We identified 8 immunogenic, antigenic, non-allergenic, non-toxic, stable and IFN-y inducing CD8 proteins for nsp3, 4 for nsp12, 11 for ORF3a and 3 for ORF9b that are common across four lineages of variants of concern: B.1.1.7, P.1, B.1.351 and B.1.617.2, which protect 98.12%, 87.08%, 96.07% and 63.8% of the world population, respectively. We also identified variant specific T cell epitopes that could be useful in targeting each variant strain separately. Including the prediction of mouse MHC affinity towards our top CD8 epitopes, our study revealed a total of 3 immunogenic, antigenic, non-allergenic, non-toxic, stable and IFN-y inducing CD8 epitopes overlapping with 6 antigenic, non-allergenic, non-toxic, stable and IFN-y inducing CD4 epitopes across all four variants of concern which can effectively be utilized in pre-clinical studies. The landscape of SARS-CoV-2 T cell epitopes that we identified can help lead SARS-CoV-2 vaccine development as well as epitope-based peptide vaccine research in the future.

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 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 Peptide Vaccine Formulation Controls the Duration of Antigen Presentation and Magnitude of Tumor-Specific CD8+ T Cell Response

2018 ◽  
Vol 200 (10) ◽  
pp. 3464-3474 ◽  
Author(s):  
Hiep Khong ◽  
Annika Volmari ◽  
Meenu Sharma ◽  
Zhimin Dai ◽  
Chinonye S. Imo ◽  
...  
Keyword(s):  
T Cell ◽  
Antigen Presentation ◽  
Cell Response ◽  
Peptide Vaccine ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Vaccine Formulation

scholarly journals Uncovering the Tumor Antigen Landscape: What to Know about the Discovery Process

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1660
Author(s):  
Sara Feola ◽  
Jacopo Chiaro ◽  
Beatriz Martins ◽  
Vincenzo Cerullo
Keyword(s):  
T Cell ◽  
Cancer Immunotherapy ◽  
Tumor Antigens ◽  
T Cell Response ◽  
Antigenic Peptides ◽  
T Cell Epitopes ◽  
Antigen Discovery ◽  
Future Challenges ◽  
Major Bottleneck ◽  
Therapeutic Cancer Vaccines

According to the latest available data, cancer is the second leading cause of death, highlighting the need for novel cancer therapeutic approaches. In this context, immunotherapy is emerging as a reliable first-line treatment for many cancers, particularly metastatic melanoma. Indeed, cancer immunotherapy has attracted great interest following the recent clinical approval of antibodies targeting immune checkpoint molecules, such as PD-1, PD-L1, and CTLA-4, that release the brakes of the immune system, thus reviving a field otherwise poorly explored. Cancer immunotherapy mainly relies on the generation and stimulation of cytotoxic CD8 T lymphocytes (CTLs) within the tumor microenvironment (TME), priming T cells and establishing efficient and durable anti-tumor immunity. Therefore, there is a clear need to define and identify immunogenic T cell epitopes to use in therapeutic cancer vaccines. Naturally presented antigens in the human leucocyte antigen-1 (HLA-I) complex on the tumor surface are the main protagonists in evocating a specific anti-tumor CD8+ T cell response. However, the methodologies for their identification have been a major bottleneck for their reliable characterization. Consequently, the field of antigen discovery has yet to improve. The current review is intended to define what are today known as tumor antigens, with a main focus on CTL antigenic peptides. We also review the techniques developed and employed to date for antigen discovery, exploring both the direct elution of HLA-I peptides and the in silico prediction of epitopes. Finally, the last part of the review analyses the future challenges and direction of the antigen discovery field.

scholarly journals High Throughput T Epitope Mapping and Vaccine Development

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Giuseppina Li Pira ◽  
Federico Ivaldi ◽  
Paolo Moretti ◽  
Fabrizio Manca
Keyword(s):  
T Cell ◽  
High Throughput ◽  
Epitope Mapping ◽  
Vaccine Development ◽  
Human Subjects ◽  
T Cell Response ◽  
Limiting Factor ◽  
T Cell Epitopes ◽  
Large Panels ◽  
Cell Assays

Mapping of antigenic peptide sequences from proteins of relevant pathogens recognized by T helper (Th) and by cytolytic T lymphocytes (CTL) is crucial for vaccine development. In fact, mapping of T-cell epitopes provides useful information for the design of peptide-based vaccines and of peptide libraries to monitor specific cellular immunity in protected individuals, patients and vaccinees. Nevertheless, epitope mapping is a challenging task. In fact, large panels of overlapping peptides need to be tested with lymphocytes to identify the sequences that induce a T-cell response. Since numerous peptide panels from antigenic proteins are to be screened, lymphocytes available from human subjects are a limiting factor. To overcome this limitation, high throughput (HTP) approaches based on miniaturization and automation of T-cell assays are needed. Here we consider the most recent applications of the HTP approach to T epitope mapping. The alternative or complementary use of in silico prediction and experimental epitope definition is discussed in the context of the recent literature. The currently used methods are described with special reference to the possibility of applying the HTP concept to make epitope mapping an easier procedure in terms of time, workload, reagents, cells and overall cost.

scholarly journals Sustained Specific and Cross-Reactive T Cell Responses to Zika and Dengue Virus NS3 in West Africa

2018 ◽  
Vol 92 (7) ◽  
Author(s):  
Bobby Brooke Herrera ◽  
Wen-Yang Tsai ◽  
Charlotte A. Chang ◽  
Donald J. Hamel ◽  
Wei-Kung Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Dengue Virus ◽  
Zika Virus ◽  
Cell Response ◽  
Vaccine Development ◽  
T Cell Responses ◽  
T Cell Response ◽  
Zikv Infection ◽  
Cell Responses

ABSTRACT Recent studies on the role of T cells in Zika virus (ZIKV) infection have shown that T cell responses to Asian ZIKV infection are important for protection, and that previous dengue virus (DENV) exposure amplifies the protective T cell response to Asian ZIKV. Human T cell responses to African ZIKV infection, however, remain unexplored. Here, we utilized the modified anthrax toxin delivery system to develop a flavivirus enzyme-linked immunosorbent spot (ELISPOT) assay. Using human ZIKV and DENV samples from Senegal, West Africa, our results demonstrate specific and cross-reactive T cell responses to nonstructural protein 3 (NS3). Specifically, we found that T cell responses to NS3 protease are ZIKV and DENV specific, but responses to NS3 helicase are cross-reactive. Sequential sample analyses revealed immune responses sustained many years after infection. These results have important implications for African ZIKV/DENV vaccine development, as well as for potential flavivirus diagnostics based on T cell responses. IMPORTANCE The recent Zika virus (ZIKV) epidemic in Latin America and the associated congenital microcephaly and Guillain-Barré syndrome have raised questions as to why we have not recognized these distinct clinical diseases in Africa. The human immunologic response to ZIKV and related flaviviruses in Africa represents a research gap that may shed light on the mechanisms contributing to protection. The goal of our study was to develop an inexpensive assay to detect and characterize the T cell response to African ZIKV and DENV. Our data show long-term specific and cross-reactive human immune responses against African ZIKV and DENV, suggesting the usefulness of a diagnostic based on the T cell response. Additionally, we show that prior flavivirus exposure influences the magnitude of the T cell response. The identification of immune responses to African ZIKV and DENV is of relevance to vaccine development.

scholarly journals TLR agonists activate HPV11 E7-pulsed DCs to promote a specific T cell response in a murine model

2011 ◽  
Vol 56 (No. 12) ◽  
pp. 602-611 ◽  
Author(s):  
XH Mao ◽  
XZ Chen ◽  
WW Zhang ◽  
JY Wang ◽  
LF Liu ◽  
...  
Keyword(s):  
T Cell ◽  
Mouse Model ◽  
Cytokine Production ◽  
T Cell Response ◽  
Antigenic Peptides ◽  
Epitope Peptide ◽  
Tlr Agonists ◽  
Ctl Epitope ◽  
Th1 Cytokine

: Some TLR agonists may up-regulate the activation of dendritic cells caused by viral antigenic peptides and antigen-specific cytotoxic T lymphocytes, which are crucial in HPV vaccine development. We investigated the ability of three TLR agonists, imiquimod, PIC and CpG, to stimulate the maturation of murine BM-DCs loaded with HPV11E7 CTL epitopes, and the subsequent effect on HPV-specific T cell responses and tumour protection in a C57BL/6 mouse model. We found that TLR agonists, mostly PIC and imiquimod, stimulated the maturation of BM-DCs pulsed with HPV11E7 CTL epitope peptide. In combination with the epitope peptide, the TLR agonists CPG and PIC augmented epitope-specific Th1 cytokine production in vivo, while imiquimod and CPG, but not PIC, enhanced Th1 cytokine production in vitro. However, we failed to observe in vivo CTL cytotoxicity and anti-tumour protection upon TLR ligation in our mouse model. Our results demonstrate that TLR agonists activate HPV11E7 CTL epitope pulsed BM-DCs to promote specific Th1 immunity in C57BL/6 mouse model, indicating the promise of TLR agonists as adjuvants for HPV epitope/DC-based multifaceted vaccines against HPV infections such as condyloma accuminatum.  

scholarly journals Archaeosome Adjuvant Overcomes Tolerance to Tumor-Associated Melanoma Antigens Inducing Protective CD8+T Cell Responses

2010 ◽  
Vol 2010 ◽  
pp. 1-13 ◽  
Author(s):  
Lakshmi Krishnan ◽  
Lise Deschatelets ◽  
Felicity C. Stark ◽  
Komal Gurnani ◽  
G. Dennis Sprott
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Regulatory Cells ◽  
T Cell Responses ◽  
T Cell Response ◽  
Antigen Delivery ◽  
Antigenic Peptides ◽  
Cell Responses ◽  
Tumor Protection ◽  
Melanoma Antigens

Vesicles comprised of the ether glycerolipids of the archaeonMethanobrevibacter smithii(archaeosomes) are potent adjuvants for evoking CD8+T cell responses. We therefore explored the ability of archaeosomes to overcome immunologic tolerance to self-antigens. Priming and boosting of mice with archaeosome-antigen evoked comparable CD8+T cell response and tumor protection to an alternate boosting strategy utilizing live bacterial vectors for antigen delivery. Vaccination with melanoma antigenic peptides TRP181-189and Gp10025-33delivered in archaeosomes resulted in IFN-γproducing antigen-specific CD8+T cells with strong cytolytic capability and protection against subcutaneous B16 melanoma. Targeting responses against multiple antigens afforded prolonged median survival against melanoma challenge. Entrapment of multiple peptides within the same vesicle or admixed formulations were both effective at evoking CD8+T cells against each antigen. Melanoma-antigen archaeosome formulations also afforded therapeutic protection against established B16 tumors when combined with depletion of T-regulatory cells. Overall, we demonstrate that archaeosome adjuvants constitute an effective choice for formulating cancer vaccines.

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