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

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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Vaccine Design against Coronavirus Spike (S) Glycoprotein in Chicken: Immunoinformatic and Computational Approaches

10.21203/rs.3.rs-25375/v1 ◽

2020 ◽

Author(s):

Sumaia Awad Elkariem Ali ◽

Eman Ali Awadelkareem

Keyword(s):

T Cell ◽

B Cell ◽

Rna Virus ◽

Economic Loss ◽

T Cell Epitopes ◽

Resistance Response ◽

Docking Analysis ◽

S Protein ◽

Infectious Bronchitis ◽

Mhc Alleles

Abstract Background: Infectious bronchitis (IB) is a highly contagious respiratory disease in chickens and produces economic loss within the poultry industry. It is caused by a single stranded RNA virus belonging to Cronaviridae family. Methods: The present study used various tools in Immune Epitope Database (IEDB) to predict conserved B and T cell epitopes against IBV spike (S) protein that may perform a significant role in provoking the resistance response to IBV infection. Results: In B cell prediction methods, three epitopes (1139KKSSYY1144, 1140KSSYYT1145, 1141SSYYT1145) were selected as surface, linear and antigenic epitopes. Many MHCI and MHCII epitopes were predicted for IBV S protein. Among them 982YYITARDMY990 and 983YITARDMYM991 epitopes displayed high antigenicity, no allergenicity and no toxicity as well as great linkage with MHCI and MHCII alleles. Moreover, docking analysis of MHCI epitope produced strong binding affinity with BF2 alleles. Conclusion: Five conserved epitopes were expected from spike glycoprotein of IBV as the best B cell and T cell epitopes due to high antigenicity, no allergenicity and no toxicity. In addition, MHC epitopes showed great linkage with MHC alleles as well as strong interaction with BF2 alleles. These epitopes should be designed and incorporated and then tested as multi-epitope vaccine against IBV.

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SARS-CoV-2 Spike Protein Evolution may Cause Difficulties for Vaccine

10.21203/rs.3.rs-80010/v1 ◽

2020 ◽

Author(s):

Jian Zhou ◽

Sun Jingjing ◽

Gang Lu ◽

Wanchun Wang ◽

Lin Wang

Keyword(s):

T Cell ◽

B Cell ◽

3D Model ◽

Bioinformatics Analysis ◽

Cell Epitope ◽

Amino Acid Sequences ◽

T Cell Epitopes ◽

Sequence Structure ◽

B Cell Epitopes ◽

S Protein

Abstract Background: Coronavirus disease 2019 (COVID-19) poses a great threat to human health and life. We performed a bioinformatics analysis to compare the sequence, structure, and epitopes of SARS-CoV-2 spike (S) protein in 10 different countries. Methods: The amino acid sequences of SARS-CoV-2 S protein were obtained from the NCBI database. We used DNASTAR Lasergene software to analyze the protein’s secondary structures. SWISS-MODEL combined with VMD software was used to construct a 3D model of SARS-CoV-2 S protein. DNASTAR Protean and the IEDB database were used to analyze the B cell epitopes and T cell epitopes, respectively. Results: The results of B cell epitopes analysis indicated that the epitopes of SARS-CoV-2 S protein in Korea and American increased, which suggested that the antigenicity of SARS-CoV-2 in Czech, Korea and American might be enhanced. A small number of B cell epitopes disappeared in the SARS-CoV-2 S protein sequence from Greece, Australia, Sweden and India, which suggested that the antigenicity of SARS-CoV-2 in Greece, Australia, Sweden and India may be weakened. T cell epitope analysis indicated that the antigenicity of SARS-CoV-2 in Czech, Korea and American was enhanced, while antigenicity of SARS-CoV-2 in Greece, Australia, Inida, Sweden and Thailand may be weakened. The sequence of SARS-CoV-2 S protein has changed as the virus has spread, and the structures and epitopes have changed accordingly. Conclusion: The mutation leads to a decrease in the antigenicity of SARS-CoV-2, which may be a mechanism for the virus to evade surveillance by the immune system.

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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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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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Structural modeling and conserved epitopes prediction against SARS-COV-2 structural proteins for vaccine development

10.21203/rs.2.23973/v1 ◽

2020 ◽

Cited By ~ 3

Author(s):

Muhammad Tahir ul Qamar ◽

Farah Shahid ◽

Usman Ali Ashfaq ◽

Sidra Aslam ◽

Israr Fatima ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Mhc Class I ◽

Mhc Class Ii ◽

Class Ii ◽

Class I ◽

Structural Proteins ◽

Severe Illness ◽

T Cell Epitopes ◽

B Cell Epitopes

Abstract Background: Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Corona virus 2 (SARS-COV-2) was first diagnosed in December 2019, Wuhan, China. Little is known about this new virus and it has the potential to cause severe illness and pneumonia in some people, therefore the development of an effective vaccine is highly desired.Methods: Immunoinformatics and statistical approaches were used in this study to forecast B- and T- cell epitopes for the SARS-COV-2 structural proteins (Surface glycoprotein, Envelope protein, and Membrane glycoprotein) that may play a key role in eliciting immune response against COVID-19. Different types of B cell epitopes (linear as well as discontinuous) and T cell (MHC class I and MHC class II) were determined. Moreover, their antigenicity and allergenicity were also estimated.Results: The antigenic B-cell epitopes exposed to the outer surface were screened out and 23 linear B cell epitopes were selected. “SPTKLNDLCFTNVY” had the highest antigenicity score among B cell epitopes. The T-cell epitopes bound to multiple alleles, antigenic, non-allergen, non-toxic, and conserved in the protein sequence were shortlisted. In total, 16 epitopes (9 from MHC class I and 7 from MHC class II) were selected. Among the T-cell epitopes, MHC class I (IPFAMQMAYRFN) and MHC class II (VTLACFVLAAVYRIN) were classified as strongly antigenic. Digestion analysis verified the safety and stability of the peptides predicted during this study. Furthermore, docking analyses of predicted peptides showed significant interactions with the HLA-B7 allele.Conclusion: The putative antigen epitopes identified in this study may serve as vaccine candidates and can help to eliminate/control growing health threat of COVID-19.

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Vaccine Design against Coronavirus Spike (S) Glycoprotein in Chicken: Immunoinformatic and Computational Approaches

10.21203/rs.3.rs-22601/v1 ◽

2020 ◽

Author(s):

Sumaia Awad Elkariem Ali ◽

Eman Ali Awadelkareem

Keyword(s):

T Cell ◽

B Cell ◽

Rna Virus ◽

Homology Modelling ◽

Economic Loss ◽

T Cell Epitopes ◽

Resistance Response ◽

Docking Analysis ◽

S Protein ◽

Mhc Alleles

Abstract BackgroundInfectious bronchitis (IB) is a highly contagious respiratory disease in chickens and produces economic loss within the poultry industry. It is caused by a single stranded RNA virus belonging to Cronaviridae family.MethodsThe present study used various tools in Immune Epitope Database (IEDB) to predict conserved B and T cell epitopes against IBV spike (S) protein that may perform a significant role in provoking the resistance response to IBV infection. Structural analysis, homology modelling and molecular docking were also achieved.ResultsIn B cell prediction methods, three epitopes (1139KKSSYY1144, 1140KSSYYT1145, 1141SSYYT1145) were selected as surface, linear and antigenic epitopes based on the length and antigenicity score. Many MHCI and MHCII epitopes were predicted for IBV S protein. Among them 982YYITARDMY990 and 983YITARDMYM991 epitopes displayed high antigenicity, no allergenicity and no toxicity as well as great linkage with MHCI and MHCII alleles. Moreover, docking analysis of MHCI epitope produced strong binding affinity with BF2 alleles. Conclusion: Five conserved epitopes were expected from spike glycoprotein of IBV as the top B cell and T cell epitopes due to high antigenicity, no allergenicity and no toxicity. In addition, MHC epitopes showed great linkage with MHC alleles as well as strong interaction with BF2 alleles. These epitopes should be designed and incorporated and then tested as multi-epitope vaccine against IBV.

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Immunoinformatic Analysis of T- and B-Cell Epitopes for SARS-CoV-2 Vaccine Design

Vaccines ◽

10.3390/vaccines8030355 ◽

2020 ◽

Vol 8 (3) ◽

pp. 355 ◽

Cited By ~ 6

Author(s):

Dongliang Wang ◽

Jinhui Mai ◽

Wenfeng Zhou ◽

Wanting Yu ◽

Yang Zhan ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Point Mutations ◽

Vaccine Design ◽

T Cell Epitopes ◽

B Cell Epitopes ◽

S Protein ◽

3D Structures ◽

3 Dimensional ◽

Immune Evasion Mechanism

Currently, there is limited knowledge about the immunological profiles of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). We used computer-based immunoinformatic analysis and the newly resolved 3-dimensional (3D) structures of the SARS-CoV-2 S trimeric protein, together with analyses of the immunogenic profiles of SARS-CoV, to anticipate potential B-cell and T-cell epitopes of the SARS-CoV-2 S protein for vaccine design, particularly for peptide-driven vaccine design and serological diagnosis. Nine conserved linear B-cell epitopes and multiple discontinuous B-cell epitopes composed of 69 residues on the surface of the SARS-CoV-2 trimeric S protein were predicted to be highly antigenic. We found that the SARS-CoV-2 S protein has a different antigenic profile than that of the SARS-CoV S protein due to the variations in their primary and 3D structures. Importantly, SARS-CoV-2 may exploit an immune evasion mechanism through two point mutations in the critical and conserved linear neutralization epitope (overlap with fusion peptide) around a sparsely glycosylated area. These mutations lead to a significant decrease in the antigenicity of this epitope in the SARS-CoV-2 S protein. In addition, 62 T-cell epitopes in the SARS-CoV-2 S protein were predicted in our study. The structure-based immunoinformatic analysis for the SARS-CoV-2 S protein in this study may improve vaccine design, diagnosis, and immunotherapy against the pandemic of COVID-19.

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A Multiple Antigen Peptide Vaccine Containing CD4+ T Cell Epitopes Enhances Humoral Immunity against Trichinella spiralis Infection in Mice

Journal of Immunology Research ◽

10.1155/2020/2074803 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14 ◽

Cited By ~ 1

Author(s):

Yuan Gu ◽

Ximeng Sun ◽

Jingjing Huang ◽

Bin Zhan ◽

Xinping Zhu

Keyword(s):

T Cell ◽

B Cell ◽

Trichinella Spiralis ◽

Peptide Vaccine ◽

Cell Epitope ◽

Muscle Larva ◽

T Cell Epitopes ◽

Protein Vaccine ◽

B Cell Epitopes ◽

Multiple Antigen

Multiepitope peptide vaccine has some advantages over traditional recombinant protein vaccine due to its easy and fast production and possible inclusion of multiple protective epitopes of pathogens. However, it is usually poorly immunogenic and needs to conjugate to a large carrier protein. Peptides conjugated to a central lysine core to form multiple antigen peptides (MAPs) will increase the immunogenicity of peptide vaccine. In this study, we constructed a MAP consisting of CD4+ T cell and B cell epitopes of paramyosin (Pmy) of Trichinella spiralis (Ts-Pmy), which has been proved to be a good vaccine candidate in our previous work. The immunogenicity and induced protective immunity of MAP against Trichinella spiralis (T. spiralis) infection were evaluated in mice. We demonstrated that mice immunized with MAP containing CD4+ T cell and B cell epitopes (MAP-TB) induced significantly higher protection against the challenge of T. spiralis larvae (35.5% muscle larva reduction) compared to the MAP containing B cell epitope alone (MAP-B) with a 12.4% muscle larva reduction. The better protection induced by immunization of MAP-TB was correlated with boosted antibody titers (both IgG1 and IgG2a) and mixed Th1/Th2 cytokine production secreted by the splenocytes of immunized mice. Further flow cytometry analysis of lymphocytes in spleens and draining lymph nodes demonstrated that mice immunized with MAP-TB specifically enhanced the generation of T follicular helper (Tfh) cells and germinal center (GC) B cells, while inhibiting follicular regulatory CD4+ T (Tfr) cells and regulatory T (Treg) cells. Immunofluorescence staining of spleen sections also confirmed that MAP-TB vaccination enhanced the formation of GCs. Our results suggest that CD4+ T cell epitope of Ts-Pmy is crucial in vaccine component for inducing better protection against T. spiralis infection.

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Anaplasma marginale Major Surface Protein 2 CD4+-T-Cell Epitopes Are Evenly Distributed in Conserved and Hypervariable Regions (HVR), Whereas Linear B-Cell Epitopes Are Predominantly Located in the HVR

Infection and Immunity ◽

10.1128/iai.72.12.7360-7366.2004 ◽

2004 ◽

Vol 72 (12) ◽

pp. 7360-7366 ◽

Cited By ~ 35

Author(s):

Jeffrey R. Abbott ◽

Guy H. Palmer ◽

Chris J. Howard ◽

Jayne C. Hope ◽

Wendy C. Brown

Keyword(s):

T Cell ◽

B Cell ◽

Surface Protein ◽

Anaplasma Marginale ◽

T Cell Epitopes ◽

B Cell Epitopes ◽

Major Surface Protein ◽

Hypervariable Regions ◽

Major Surface ◽

Linear B

ABSTRACT Organisms in the genus Anaplasma express an immunodominant major surface protein 2 (MSP2), composed of a central hypervariable region (HVR) flanked by highly conserved regions. Throughout Anaplasma marginale infection, recombination results in the sequential appearance of novel MSP2 variants and subsequent control of rickettsemia by the immune response, leading to persistent infection. To determine whether immune evasion and selection for variant organisms is associated with a predominant response against HVR epitopes, T-cell and linear B-cell epitopes were localized by measuring peripheral blood gamma interferon-secreting cells, proliferation, and antibody binding to 27 overlapping peptides spanning MSP2 in 16 cattle. Similar numbers of MSP2-specific CD4+ T-cell epitopes eliciting responses of similar magnitude were found in conserved and hypervariable regions. T-cell epitope clusters recognized by the majority of animals were identified in the HVR (amino acids [aa] 171 to 229) and conserved regions (aa 101 to 170 and 272 to 361). In contrast, linear B-cell epitopes were concentrated in the HVR, residing within hydrophilic sequences. The pattern of recognition of epitope clusters by T cells and of HVR epitopes by B cells is consistent with the influence of protein structure on epitope recognition.

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The Antigenic Topology of Norovirus as Defined by B and T Cell Epitope Mapping: Implications for Universal Vaccines and Therapeutics

Viruses ◽

10.3390/v11050432 ◽

2019 ◽

Vol 11 (5) ◽

pp. 432 ◽

Cited By ~ 6

Author(s):

Jessica M. van Loben Sels ◽

Kim Y. Green

Keyword(s):

T Cell ◽

B Cell ◽

Cell Epitope ◽

T Cell Epitopes ◽

B Cell Epitopes ◽

P Domain ◽

Capsid Protein Vp1 ◽

Murine Noroviruses ◽

Acute Nonbacterial Gastroenteritis ◽

Insight Into

Human norovirus (HuNoV) is the leading cause of acute nonbacterial gastroenteritis. Vaccine design has been confounded by the antigenic diversity of these viruses and a limited understanding of protective immunity. We reviewed 77 articles published since 1988 describing the isolation, function, and mapping of 307 unique monoclonal antibodies directed against B cell epitopes of human and murine noroviruses representing diverse Genogroups (G). Of these antibodies, 91, 153, 21, and 42 were reported as GI-specific, GII-specific, MNV GV-specific, and G cross-reactive, respectively. Our goal was to reconstruct the antigenic topology of noroviruses in relationship to mapped epitopes with potential for therapeutic use or inclusion in universal vaccines. Furthermore, we reviewed seven published studies of norovirus T cell epitopes that identified 18 unique peptide sequences with CD4- or CD8-stimulating activity. Both the protruding (P) and shell (S) domains of the major capsid protein VP1 contained B and T cell epitopes, with the majority of neutralizing and HBGA-blocking B cell epitopes mapping in or proximal to the surface-exposed P2 region of the P domain. The majority of broadly reactive B and T cell epitopes mapped to the S and P1 arm of the P domain. Taken together, this atlas of mapped B and T cell epitopes offers insight into the promises and challenges of designing universal vaccines and immunotherapy for the noroviruses.

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