Identification of B-cell epitopes on the betanodavirus capsid protein

Human norovirus (HuNoV) is the leading cause of nonbacterial gastroenteritis worldwide with the GII.4 genotype accounting for over 80% of infections. The major capsid protein of GII.4 variants is evolving rapidly, resulting in new epidemic variants with altered antigenic potentials that must be considered for the development of an effective vaccine. In this study, we identify and characterize linear blockade B-cell epitopes in HuNoV GII.4. Five unique linear B-cell epitopes, namely P2A, P2B, P2C, P2D, and P2E, were predicted on the surface-exposed regions of the capsid protein. Evolving of the surface-exposed epitopes over time was found to correlate with the emergence of new GII.4 outbreak variants. Molecular dynamic simulation (MD) analysis and molecular docking revealed that amino acid substitutions in the putative epitopes P2B, P2C, and P2D could be associated with immune escape and the appearance of new GII.4 variants by affecting solvent accessibility and flexibility of the antigenic sites and histo-blood group antigens (HBAG) binding. Testing the synthetic peptides in wild-type mice, epitopes P2B (336–355), P2C (367–384), and P2D (390–400) were recognized as GII.4-specific linear blockade epitopes with the blocking rate of 68, 55 and 28%, respectively. Blocking rate was found to increase to 80% using the pooled serum of epitopes P2B and P2C. These data provide a strategy for expanding the broad blockade potential of vaccines for prevention of NoV infection.

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Fine mapping of linear B cell epitopes on capsid protein of porcine circovirus 3

Applied Microbiology and Biotechnology ◽

10.1007/s00253-020-10664-2 ◽

2020 ◽

Vol 104 (14) ◽

pp. 6223-6234

Author(s):

Min Jiang ◽

Junqing Guo ◽

Gaiping Zhang ◽

Qianyue Jin ◽

Yankai Liu ◽

...

Keyword(s):

B Cell ◽

Capsid Protein ◽

Fine Mapping ◽

Porcine Circovirus ◽

B Cell Epitopes ◽

Porcine Circovirus 3 ◽

Linear B

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Antigenic Determinants of Possible Vaccine Escape by Porcine Circovirus Subtype 2b Viruses

Bioinformatics and Biology Insights ◽

10.4137/bbi.s30226 ◽

2015 ◽

Vol 9s2 ◽

pp. BBI.S30226 ◽

Cited By ~ 2

Author(s):

Megan Constans ◽

Marvin Ssemadaali ◽

Oleksandr Kolyvushko ◽

Sheela Ramamoorthy

Keyword(s):

T Cell ◽

B Cell ◽

Capsid Protein ◽

Rational Design ◽

Immune Escape ◽

Clinical Signs ◽

Porcine Circovirus ◽

Antigenic Determinants ◽

B Cell Epitopes ◽

Cell Functions

Currently available commercial vaccines against porcine circovirus strain 2 (PCV2) solely target the PCV2a genotype. While PCV2 vaccines are highly effective in preventing clinical signs, PCV2b has dominated over the PCV2a genotype in prevalence, corresponding with the introduction of PCV2a vaccines. A recently emerged PCV2b recombinant with an additional amino acid in the capsid protein, designated the mutant PCV2b (mPCV2b), is cause for concern due to its increased virulence and rapid spread. The accumulation of recent evidence for the increased genetic diversity in PCV2 suggests that current vaccines against PCV2a may be inducing selection pressure and driving viral evolution. In this study, the hypothesis that differences in key immune epitopes between the PCV2a vaccine strains, a classical PCV2b strain called PCV2b 41513 obtained from a vaccine-failure case, and mPCV2b strains could promote vaccine escape was tested using immuno-informatic tools. In the major viral proteins, 9 of the 18 predicted swine leukocyte antigens (SLA) class-I epitopes, 8 of the 22 predicted SLA class-II epitopes, and 7 of the 25 predicted B cell epitopes varied between the vaccine and field strains. A majority of the substitutions in both the T- and B-cell epitopes were located in the capsid protein. Some B- and T-cell epitopes that were identified as immunogenic in the vaccine strain were not identified as epitopes in the field strains, indicating a subtle shift in the antigenic profile of the field strains. Several nonconserved epitopes had both predicted B- and T-cell functions. Therefore, substitutions in the dual epitopes could affect both arms of the immune response simultaneously, causing immune escape. Our findings support further rational design of PCV2 vaccines to increase the current threshold of protection.

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Characterization of Two Novel Linear B-Cell Epitopes in the Capsid Protein of Avian Hepatitis E Virus (HEV) That Are Common to Avian, Swine, and Human HEVs

Journal of Virology ◽

10.1128/jvi.00107-15 ◽

2015 ◽

Vol 89 (10) ◽

pp. 5491-5501 ◽

Cited By ~ 17

Author(s):

Xinjie Wang ◽

Qin Zhao ◽

Lu Dang ◽

Yani Sun ◽

Jiming Gao ◽

...

Keyword(s):

Amino Acid ◽

B Cell ◽

Capsid Protein ◽

Hepatitis E Virus ◽

Hepatitis E ◽

Antigenic Structure ◽

B Cell Epitopes ◽

Avian Hepatitis E Virus ◽

Avian Hev ◽

Linear B

ABSTRACTAntisera raised against the avian hepatitis E virus (HEV) capsid protein are cross-reactive with human and swine HEV capsid proteins. In this study, two monoclonal antibodies (MAbs) against the avian HEV capsid protein, namely, 3E8 and 1B5, were shown to cross-react with the swine HEV capsid protein. The motifs involved in binding both MAbs were identified and characterized using phage display biopanning, peptide synthesis, and truncated or mutated protein expression, along with indirect enzyme-linked immunosorbent assay (ELISA) and Western blotting. The results showed that the I/VPHD motif is a necessary core sequence and that P and H are two key amino acids for recognition by MAb 3E8. The VKLYM/TS motif is the minimal amino acid sequence necessary for recognition by MAb 1B5. Cross-reactivity between the two epitopes and antibodies against avian, swine, and human HEVs in sera showed that both epitopes are common to avian, swine, and human HEVs. In addition, amino acid sequence alignment of the capsid proteins revealed that the key motifs of both novel epitopes are the same in HEVs from different animal species, predicting that they may be common to HEV isolates from boars, rabbits, rats, ferrets, mongooses, deer, and camels as well. Protein modeling analysis showed that both epitopes are at least partially exposed on the surface of the HEV capsid protein. Protective capacity analysis demonstrated that the two epitopes are nonprotective against avian HEV infection in chickens. Collectively, these studies characterize two novel linear B-cell epitopes common to avian, swine, and human HEVs, which furthers the understanding of HEV capsid protein antigenic structure.IMPORTANCEMore and more evidence indicates that the host range diversity of hepatitis E virus (HEV) is a global public health concern. A better understanding of the antigenic structure of the HEV capsid protein may improve disease diagnosis and prevention. In this study, binding site mapping and localization as well as the antigenic biology of two novel linear B-cell epitopes common to several different species of HEV were characterized. These findings partially reveal the antigenic structure of the HEV capsid protein and provide potential applications for the development of diagnostics and interventions for HEV infection.

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