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 Impact of glycan cloud on the B-cell epitope prediction of SARS-CoV-2 Spike protein

npj Vaccines ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
René Wintjens ◽  
Amanda Makha Bifani ◽  
Pablo Bifani
Keyword(s):  
B Cell ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
Spike Protein ◽  
B Cell Epitope

scholarly journals Emergence of Drift Variants That May Affect COVID-19 Vaccine Development and Antibody Treatment

Pathogens ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 324 ◽  
Author(s):  
Takahiko Koyama ◽  
Dilhan Weeraratne ◽  
Jane L. Snowdon ◽  
Laxmi Parida
Keyword(s):  
Rna Polymerase ◽  
B Cell ◽  
Genetic Drift ◽  
Vaccine Development ◽  
Cell Epitope ◽  
Spike Protein ◽  
Immune Recognition ◽  
T Cell Epitopes ◽  
Antibody Treatment ◽  
B Cell Epitope

New coronavirus (SARS-CoV-2) treatments and vaccines are under development to combat COVID-19. Several approaches are being used by scientists for investigation, including (1) various small molecule approaches targeting RNA polymerase, 3C-like protease, and RNA endonuclease; and (2) exploration of antibodies obtained from convalescent plasma from patients who have recovered from COVID-19. The coronavirus genome is highly prone to mutations that lead to genetic drift and escape from immune recognition; thus, it is imperative that sub-strains with different mutations are also accounted for during vaccine development. As the disease has grown to become a pandemic, B-cell and T-cell epitopes predicted from SARS coronavirus have been reported. Using the epitope information along with variants of the virus, we have found several variants which might cause drifts. Among such variants, 23403A>G variant (p.D614G) in spike protein B-cell epitope is observed frequently in European countries, such as the Netherlands, Switzerland, and France, but seldom observed in China.

scholarly journals Identification of a novel B-cell epitope in the spike protein of porcine epidemic diarrhea virus

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Ning Kong ◽  
Qiong Meng ◽  
Yajuan Jiao ◽  
Yongguang Wu ◽  
Yewen Zuo ◽  
...  
Keyword(s):  
B Cell ◽  
Porcine Epidemic Diarrhea Virus ◽  
Cell Epitope ◽  
Spike Protein ◽  
Diarrhea Virus ◽  
B Cell Epitope ◽  
Porcine Epidemic Diarrhea

scholarly journals In silico analysis suggests less effective MHC-II presentation of SARS-CoV-2 RBM peptides: Implication for neutralizing antibody responses

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246731
Author(s):  
Andrea Castro ◽  
Kivilcim Ozturk ◽  
Maurizio Zanetti ◽  
Hannah Carter
Keyword(s):  
T Cell ◽  
B Cell ◽  
Neutralizing Antibodies ◽  
Cell Epitope ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Binding Motif ◽  
T Cell Epitopes ◽  
Mhc Ii ◽  
B Cell Epitope

SARS-CoV-2 antibodies develop within two weeks of infection, but wane relatively rapidly post-infection, raising concerns about whether antibody responses will provide protection upon re-exposure. Here we revisit T-B cooperation as a prerequisite for effective and durable neutralizing antibody responses centered on a mutationally constrained RBM B cell epitope. T-B cooperation requires co-processing of B and T cell epitopes by the same B cell and is subject to MHC-II restriction. We evaluated MHC-II constraints relevant to the neutralizing antibody response to a mutationally-constrained B cell epitope in the receptor binding motif (RBM) of the spike protein. Examining common MHC-II alleles, we found that peptides surrounding this key B cell epitope are predicted to bind poorly, suggesting a lack MHC-II support in T-B cooperation, impacting generation of high-potency neutralizing antibodies in the general population. Additionally, we found that multiple microbial peptides had potential for RBM cross-reactivity, supporting previous exposures as a possible source of T cell memory.

Identification of human linear B-cell epitope sites on the envelope glycoproteins of Crimean-Congo haemorrhagic fever virus

2014 ◽  
Vol 143 (7) ◽  
pp. 1451-1456 ◽  
Author(s):  
D. GOEDHALS ◽  
J. T. PAWESKA ◽  
F. J. BURT
Keyword(s):  
B Cell ◽  
Cell Epitope ◽  
Fever Virus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Haemorrhagic Fever ◽  
Serum Samples ◽  
B Cell Epitope ◽  
Crimean Congo Haemorrhagic Fever ◽  
Peptide G ◽  
Linear B

SUMMARYA peptide library was used to screen for regions containing potential linear B-cell epitope sites in the glycoproteins and nucleoprotein of Crimean-Congo haemorrhagic fever virus (CCHFV) in an enzyme-linked immunosorbent assay (ELISA). The library consisted of 156 peptides, spanning the nucleoprotein and mature GN and GC proteins in a 19-mer with 9-mer overlap format. Using pooled serum samples from convalescent patients to screen the library, six peptides were identified as potential epitope sites. Further testing of these six peptides with individual patient sera identified two of these peptides as probable epitope sites, with peptide G1451–1469 reacting to 13/15 and peptide G1613–1631 to 14/15 human sera. These peptides are situated on the GC protein at amino acid positions 1451–1469 (relative to CCHFV isolate SPU103/97) (TCTGCYACSSGISCKVRIH) and 1613–1631 (FMFGWRILFCFKCCRRTRG). Identified peptides may have application in ELISA for diagnostic or serosurveillance purposes.

scholarly journals Identification of four linear B-cell epitopes on the SARS-CoV-2 spike protein able to elicit neutralizing antibodiesIdentification of four linear B-cell epitopes on the SARS-CoV-2 spike protein able to elicit neutralizing antibodies

2021 ◽  
Author(s):  
Lin Li ◽  
Zhongpeng Zhao ◽  
Xiaolan Yang ◽  
Wendong Li ◽  
Shaolong Chen ◽  
...  
Keyword(s):  
B Cell ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Cell Epitope ◽  
Spike Protein ◽  
Effective Vaccine ◽  
B Cell Epitopes ◽  
S Protein ◽  
B Cell Epitope ◽  
Linear B

Abstract SARS-CoV-2 unprecedentedly threatens the public health at worldwide level. There is an urgent need to develop an effective vaccine within a highly accelerated time. Here, we present the most comprehensive S-protein-based linear B-cell epitope candidate list by combining epitopes predicted by eight widely-used immune-informatics methods with the epitopes curated from literature published between Feb 6, 2020 and July 10, 2020. We find four top prioritized linear B-cell epitopes in the hotspot regions of S protein can specifically bind with pooled serum antibodies from horses, mice, and monkeys inoculated with different SARS-CoV-2 vaccine candidates or five patients recovering from COVID-19. The four linear B-cell epitopes can induce neutralizing antibodies against both pseudo and live SARS-CoV-2 virus in immunized wild-type BALB/c mice. This study suggests that the four linear B-cell epitopes are potentially important candidates for serological assay or vaccine development.

scholarly journals Identification of a dengue virus type 2 (DEN-2) serotype-specific B-cell epitope and detection of DEN-2-immunized animal serum samples using an epitope-based peptide antigen

2003 ◽  
Vol 84 (10) ◽  
pp. 2771-2779 ◽  
Author(s):  
Han-Chung Wu ◽  
Mei-Ying Jung ◽  
Chien-Yu Chiu ◽  
Ting-Ting Chao ◽  
Szu-Chia Lai ◽  
...  
Keyword(s):  
Dengue Virus ◽  
B Cell ◽  
Virus Type ◽  
Synthetic Peptide ◽  
Cell Epitope ◽  
Serum Samples ◽  
Peptide Antigen ◽  
B Cell Epitope ◽  
Dengue Virus Type 2

In this study, a serotype-specific monoclonal antibody (mAb), D2 16-1 (Ab4), against dengue virus type 2 (DEN-2) was generated. The specificity of Ab4, which recognized DEN-2 non-structural protein 1, was determined by ELISA, immunofluorescence and immunoblotting analyses. The serotype-specific B-cell epitope of Ab4 was identified further from a random phage-displayed peptide library; selected phage clones reacted specifically with Ab4 and did not react with other mAbs. Immunopositive phage clones displayed a consensus motif, His–Arg/Lys–Leu/Ile, and a synthetic peptide corresponding to the phage-displayed peptide bound specifically to Ab4. The His and Arg residues in this epitope were found to be crucial for peptide binding to Ab4 and binding activity decreased dramatically when these residues were changed to Leu. The epitope-based synthetic peptide not only identified serum samples from DEN-2-immunized mice and rabbits by ELISA but also differentiated clearly between serum samples from DEN-2- and Japanese encephalitis virus-immunized mice. This mAb and its epitope-based peptide antigen will be useful for serologic diagnosis of DEN-2 infection. Furthermore, DEN-2 epitope identification makes it feasible to dissect antibody responses to DEN and to address the role of antibodies in the pathogenesis of primary and secondary DEN-2 infections.

scholarly journals MHC-II constrains the natural neutralizing antibody response to the SARS-CoV-2 spike RBM in humans

2020 ◽  
Author(s):  
Andrea Castro ◽  
Kivilcim Ozturk ◽  
Maurizio Zanetti ◽  
Hannah Carter
Keyword(s):  
T Cell ◽  
Antibody Response ◽  
B Cell ◽  
Neutralizing Antibodies ◽  
Cell Epitope ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Binding Motif ◽  
Mhc Ii ◽  
B Cell Epitope

AbstractSARS-CoV-2 antibodies develop within two weeks of infection, but wane relatively rapidly post-infection, raising concerns about whether antibody responses will provide protection upon re-exposure. Here we revisit T-B cooperation as a prerequisite for effective and durable neutralizing antibody responses centered on a mutationally constrained RBM B cell epitope. T-B cooperation requires co-processing of B and T cell epitopes by the same B cell and is subject to MHC-II restriction. We evaluated MHC-II constraints relevant to the neutralizing antibody response to a mutationally-constrained B cell epitope in the receptor binding motif (RBM) of the spike protein. Examining common MHC-II alleles, we found that peptides surrounding this key B cell epitope are predicted to bind poorly, suggesting a lack MHC-II support in T-B cooperation, impacting generation of high-potency neutralizing antibodies in the general population. Additionally, we found that multiple microbial peptides had potential for RBM cross-reactivity, supporting previous exposures as a possible source of T cell memory.Graphical abstract

scholarly journals Emergence of Drift Variants That May Affect COVID-19 Vaccine Development and Antibody Treatment

2020 ◽  
Author(s):  
Takahiko Koyama ◽  
Dilhan Weeraratne ◽  
Jane L. Snowdon ◽  
Laxmi Parida
Keyword(s):  
Rna Polymerase ◽  
B Cell ◽  
Genetic Drift ◽  
Vaccine Development ◽  
Cell Epitope ◽  
Spike Protein ◽  
Immune Recognition ◽  
T Cell Epitopes ◽  
Antibody Treatment ◽  
B Cell Epitope

New coronavirus (SARS-CoV-2) treatments and vaccines are under development to combat the COVID-19 disease. Several approaches are being used by scientists for investigation including 1) various small molecule approaches targeting RNA polymerase, 3C-like protease, and RNA endonuclease and 2) exploration of antibodies obtained from convalescent plasma from patients who have recovered from COVID-19. The coronavirus genome is highly prone to mutations that lead to genetic drift and escape from immune recognition; thus, it is imperative that sub-strains with different mutations are also accounted for during vaccine development. As the disease has grown to become a pandemic, new B-cell and T-cell epitopes predicted from SARS coronavirus have been reported. Using the epitope information along with variants of the virus, we have found several variants which might cause drifts. Among such variants, 23403A&gt;G variant (p.D614G) in spike protein B-cell epitope is observed frequently in European countries such as the Netherlands, Switzerland and France.

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