scholarly journals Seropositive reaction rates of 9 B cell epitopes of the SARS-CoV-2 spike protein and the relationship between the epitopes and neutralizing antibody

Intervirology ◽  
2021 ◽  
Author(s):  
Li Zhu ◽  
Yunwen Zhang ◽  
Zhengrong Yang ◽  
Baisheng Li ◽  
Tiejian Feng ◽  
...  
Keyword(s):  
B Cell ◽  
Neutralizing Antibody ◽  
Reaction Rates ◽  
Spike Protein ◽  
B Cell Epitopes ◽  
The Relationship

scholarly journals The influence of major S protein mutations of SARS-CoV-2 on the potential B cell epitopes

2020 ◽  
Author(s):  
Xianlin Yuan ◽  
liangping li
Keyword(s):  
B Cell ◽  
Large Scale ◽  
Population Change ◽  
Vaccine Development ◽  
Rna Virus ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Common Variants ◽  
B Cell Epitopes ◽  
S Protein

AbstractSARS-CoV-2 has rapidly transmitted worldwide and results in the COVID-19 pandemic. Spike glycoprotein on surface is a key factor of viral transmission, and has appeared a lot of variants due to gene mutations, which may influence the viral antigenicity and vaccine efficacy. Here, we used bioinformatic tools to analyze B-cell epitopes of prototype S protein and its 9 common variants. 12 potential linear and 53 discontinuous epitopes of B-cells were predicted from the S protein prototype. Importantly, by comparing the epitope alterations between prototype and variants, we demonstrate that B-cell epitopes and antigenicity of 9 variants appear significantly different alterations. The dominant D614G variant impacts the potential epitope least, only with moderately elevated antigenicity, while the epitopes and antigenicity of some mutants(V483A, V367F, etc.) with small incidence in the population change greatly. These results suggest that the currently developed vaccines should be valid for a majority of SARS-CoV-2 infectors. This study provides a scientific basis for large-scale application of SARS-CoV-2 vaccines and for taking precautions against the probable appearance of antigen escape induced by genetic variation after vaccination.Author SummaryThe global pandemic of SARS-CoV-2 has lasted for more than half a year and has not yet been contained. Until now there is no effective treatment for SARS-CoV-2 caused disease (COVID-19). Successful vaccine development seems to be the only hope. However, this novel coronavirus belongs to the RNA virus, there is a high mutation rate in the genome, and these mutations often locate on the Spike proteins of virus, the gripper of the virus entering the cells. Vaccination induce the generation of antibodies, which block Spike protein. However, the Spike protein variants may change the recognition and binding of antibodies and make the vaccine ineffective. In this study, we predict neutralizing antibody recognition sites (B cell epitopes) of the prototype S protein of SARS-COV2, along with several common variants using bioinformatics tools. We discovered the variability in antigenicity among the mutants, for instance, in the more widespread D614G variant the change of epitope was least affected, only with slight increase of antigenicity. However, the antigenic epitopes of some mutants change greatly. These results could be of potential importance for future vaccine design and application against SARS-CoV2 variants.

scholarly journals The relationship between colonization and haemagglutination inhibiting and B cell epitopes of Porphyromonas gingivalis

1997 ◽  
Vol 110 (2) ◽  
pp. 285-291 ◽  
Author(s):  
C. G. KELLY ◽  
V. BOOTH ◽  
H. KENDAL ◽  
J. M. SLANEY ◽  
M. A. CURTIS ◽  
...  
Keyword(s):  
B Cell ◽  
Porphyromonas Gingivalis ◽  
B Cell Epitopes ◽  
The Relationship

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 A newly identified linear epitope on non-RBD region of SARS-CoV-2 spike protein improves the serological detection rate of COVID-19 patients

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yunwen Zhang ◽  
Zhengrong Yang ◽  
Sicheng Tian ◽  
Baisheng Li ◽  
Tiejian Feng ◽  
...  
Keyword(s):  
B Cell ◽  
Positive Reaction ◽  
Reaction Rate ◽  
Cell Epitope ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Serological Detection ◽  
Serum Samples ◽  
B Cell Epitope ◽  
Asymptomatic Infections

Abstract Background Serological test is helpful in confirming and tracking infectious diseases in large population with the advantage of fast and convenience. Using the specific epitope peptides identified from the whole antigen as the detection antigen is sensitive and relatively economical. The development of epitope peptide-based detection kits for COVID-19 patients requires comprehensive information about epitope peptides. But the data on B cell epitope of SARS-CoV-2 spike protein is still limited. More importantly, there is a lack of serological data on the peptides in the population. In this study, we aimed to identify the B cell epitope peptides of spike protein and detect the reactivity in serum samples, for further providing data support for their subsequent serological applications. Results Two B cell linear epitopes, P104 and P82, located in non-RBD region of SARS-CoV-2 S protein were identified by indirect ELISA screening of an overlapping peptide library of the S protein with COVID-19 patients’ convalescent serum. And the peptides were verified by testing with 165 serum samples. P104 has not been reported previously; P82 is contained in peptide S21P2 reported before. The positive reaction rates of epitope peptides S14P5 and S21P2, the two non-RBD region epitopes identified by Poh et al., and P82 and P104 were 77.0%, 73.9%, 61.2% and 30.3%, respectively, for 165 convalescent sera, including 30 asymptomatic patients. Although P104 had the lowest positive rate for total patients (30.3%), it exhibited slight advantage for detection of asymptomatic infections (36.7%). Combination of epitopes significantly improved the positive reaction rate. Among all combination patterns, (S14P5 + S21P2 + P104) pattern exhibited the highest positive reaction rate for all patients (92.7%), as well as for asymptomatic infections (86.7%), confirming the feasibility of P104 as supplementary antigen for serological detection. In addition, we analyzed the correlation between epitopes with neutralizing antibody, but only S14P5 had a medium positive correlation with neutralizing antibody titre (rs = 0.510, P < 0.01). Conclusion Our research proved that epitopes on non-RBD region are of value in serological detection especially when combination more than one epitope, thus providing serological reaction information about the four epitopes, which has valuable references for their usage.

scholarly journals Identification of Protective B-Cell Epitopes within the Novel Malaria Vaccine Candidate Plasmodium falciparum Schizont Egress Antigen 1

2017 ◽  
Vol 24 (7) ◽  
Author(s):  
Christina E. Nixon ◽  
Sangshin Park ◽  
Sunthorn Pond-Tor ◽  
Dipak Raj ◽  
Lynn E. Lambert ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
B Cell ◽  
The Novel ◽  
B Cell Epitopes ◽  
Content Type ◽  
Peptide Microarrays ◽  
Malaria Vaccine Candidate ◽  
Antibody Levels ◽  
Longitudinal Treatment ◽  
The Relationship

ABSTRACT Naturally acquired antibodies to Plasmodium falciparum schizont egress antigen 1 (PfSEA-1A) are associated with protection against severe malaria in children. Vaccination of mice with SEA-1A from Plasmodium berghei (PbSEA-1A) decreases parasitemia and prolongs survival following P. berghei ANKA challenge. To enhance the immunogenicity of PfSEA-1A, we identified five linear B-cell epitopes using peptide microarrays probed with antisera from nonhuman primates vaccinated with recombinant PfSEA-1A (rPfSEA-1A). We evaluated the relationship between epitope-specific antibody levels and protection from parasitemia in a longitudinal treatment-reinfection cohort in western Kenya. Antibodies to three epitopes were associated with 16 to 17% decreased parasitemia over an 18-week high transmission season. We are currently designing immunogens to enhance antibody responses to these three epitopes.

scholarly journals Immuno-informatics design of a multimeric epitope peptide based vaccine targeting SARS-CoV-2 spike glycoprotein

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248061
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

Developing an efficacious vaccine for SARS-CoV-2 infection is critical to stemming COVID-19 fatalities and providing the global community with immune protection. We have used a bioinformatic approach to aid in designing 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 and 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. With our In silico test, the vaccine construct was predicted to elicit high antigenicity and cell-mediated immunity when given as a homologous prime-boost, triggering of toll-like receptor 5 by the adjuvant linker. The vaccine was also 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 Bioinformatic analysis of epitope-based vaccine design against the novel SARS-COV-2

2020 ◽  
Author(s):  
Hongzhi Chen ◽  
Xiang Wu
Keyword(s):  
B Cell ◽  
Nucleocapsid Protein ◽  
Vaccine Development ◽  
Wide Spectrum ◽  
Cell Epitope ◽  
Bioinformatic Analysis ◽  
Spike Protein ◽  
B Cell Epitopes ◽  
Surface Accessibility ◽  
Binding Peptides

Abstract Background: An outbreak of infection caused by SARS-COV-2 recently has brought great challenge to public health. Rapid identification of immune epitopes would be an efficient way to screen the candidates for vaccine development at the time of an impending pandemic. This study aimed to predict the protective epitopes with bioinformatic methods and resources for vaccine development. Methods: ABCpred and BepiPred servers were utilized for sequential B-cell epitope analysis. Discontinuous B-cell epitopes were predicted via DISCTOPE server. IEDB server was utilized for HLA-1 and HLA-2 binding peptides computation. Surface accessibility, antigenicity, and other important features of forcasted epitopes were characterized for immunogen potential evaluation.Results: A total of 63 sequential B-cell epitopes on spike protein were predicted and 3 peptides (333-338, 648-663, 1064-1079) exhibited high antigenicity score and good surface accessibility in our modeling. 8 residues within spike protein (Gly184, Gly502, Lys558, Pro561, Pro809, Ser810, Lys811, Pro812) are forcasted as components of discontinuous B-cell epitopes. The bioinformatic analysis of HLA binding peptides within nucleocapsid protein produced 81 and 64 peptides being able to bind class-I and class-II molecule respectively. The peptide (104-112) has a high immunogenicity score and was predicted to bind a wide spectrum of both HLA-1 and HLA-2 molecules. Conclusions: Linear B-cell epitopes (333-338, 648-663, 1064-1079) and discontinuous B-cell epitopes (Gly184, Gly502, Lys558, Pro561, Pro809, Ser810, Lys811, Pro812) on spike protein, T-cell epitope (104-112) within nucleocapsid protein were identified and recommended for developing vaccine against SARS-COV-2.

scholarly journals Computational assessment of the spike protein antigenicity reveals diversity in B cell epitopes but stability in T cell epitopes across SARS-CoV-2 variants

2021 ◽  
Author(s):  
Anni Ge ◽  
Melissa Rioux ◽  
Alyson Ann Kelvin
Keyword(s):  
T Cell ◽  
B Cell ◽  
Glycosylation Site ◽  
Viral Escape ◽  
Spike Protein ◽  
Immune Memory ◽  
Cell Vaccine ◽  
T Cell Epitopes ◽  
B Cell Epitopes ◽  
Cell Immunity

Since its emergence into the human population at the end of 2019, SARS-CoV-2 has caused significant morbidity and mortality worldwide. Efforts to develop a protective vaccine against COVID-19 have yielded several vaccine platforms currently in distribution targeting the original SARS-CoV-2 spike protein sequence from the first cases of infection. In recent months, variants of SARS-CoV-2 have raised concerns that viral mutation may undermine vaccination efforts through viral escape of host immune memory acquired from infection or vaccination. We therefore used a computational approach to predict changes in spike protein antigenicity with respect to host B cell and CD8+ T cell immunity across six SARS-CoV-2 variants (D614G, B.1.1.7, B.1.351, P.1, B.1.429, and mink-related). Our epitope analysis using DiscoTope suggests possible changes in B cell epitopes in the S1 region of the spike protein across variants, in particular the B.1.1.7 and B.1.351 lineages, which may influence immunodominance. Additionally, we show that high-affinity MHC-I-binding peptides and glycosylation sites on the spike protein appear consistent between variants with the exception of an extra glycosylation site in the P.1 variant. Together, these analyses suggests T cell vaccine strategies have the most longevity before reformulation.

scholarly journals Bioinformatics analysis of epitope-based vaccine design against the novel SARS-CoV-2

2020 ◽  
Author(s):  
Hongzhi Chen ◽  
Lingli Tang ◽  
Xinling Yu ◽  
Jie Zhou ◽  
Yunfeng Chang ◽  
...  
Keyword(s):  
B Cell ◽  
Nucleocapsid Protein ◽  
Bioinformatics Analysis ◽  
Vaccine Development ◽  
Wide Spectrum ◽  
Cell Epitope ◽  
Spike Protein ◽  
B Cell Epitopes ◽  
Surface Accessibility ◽  
Binding Peptides

Abstract Background: An outbreak of infection caused by SARS-CoV-2 recently has brought a great challenge to public health. Rapid identification of immune epitopes would be an efficient way to screen the candidates for vaccine development at the time of pandemic. This study aimed to predict the protective epitopes with bioinformatics methods and resources for vaccine development. Methods: ABCpred and BepiPred servers were utilized for sequential B-cell epitope analysis. Discontinuous B-cell epitopes were predicted via DiscoTope 2.0 program. IEDB server was utilized for HLA-1 and HLA-2 binding peptides computation. Surface accessibility, antigenicity, and other important features of forecasted epitopes were characterized for immunogen potential evaluation. Results: A total of 63 sequential B-cell epitopes on spike protein were predicted and 4 peptides (Spike315-324, Spike333-338, Spike648-663, Spike1064-1079) exhibited high antigenicity score and good surface accessibility. 10 residues within spike protein (Gly496, Glu498, Pro499, Thr500, Leu1141, Gln1142, Pro1143, Glu1144, Leu1145, Asp1146) are forecasted as components of discontinuous B-cell epitopes. The bioinformatics analysis of HLA binding peptides within nucleocapsid protein produced 81 and 64 peptides being able to bind class-I and class-II molecule respectively. The peptides (Nucleocapsid66-75, Nucleocapsid104-112) were predicted to bind a wide spectrum of both HLA-1 and HLA-2 molecules. Conclusions: B-cell epitopes on spike protein and T-cell epitopes within nucleocapsid protein were identified and recommended for developing a protective vaccine against SARS-CoV-2.

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