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

2015 ◽  
Vol 9s2 ◽  
pp. BBI.S30226 ◽  
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.

scholarly journals Linear B-Cell Epitopes in Human Norovirus GII.4 Capsid Protein Elicit Blockade Antibodies

Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 52
Author(s):  
Hassan Moeini ◽  
Suliman Qadir Afridi ◽  
Sainitin Donakonda ◽  
Percy A. Knolle ◽  
Ulrike Protzer ◽  
...  
Keyword(s):  
B Cell ◽  
Capsid Protein ◽  
Immune Escape ◽  
Solvent Accessibility ◽  
Effective Vaccine ◽  
Blood Group Antigens ◽  
Human Norovirus ◽  
B Cell Epitopes ◽  
Blocking Rate ◽  
Linear B

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.

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

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

In silico prediction of T‐cell and B‐cell epitopes of human papillomavirus type 16 L1 protein

2021 ◽  
Author(s):  
Shahab Mahmoudvand ◽  
Somayeh Shokri ◽  
Manoochehr Makvandi ◽  
Reza Taherkhani ◽  
Mohammad Rashno ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
T Cell ◽  
B Cell ◽  
In Silico ◽  
In Silico Prediction ◽  
B Cell Epitopes ◽  
Human Papillomavirus Type 16 ◽  
L1 Protein

scholarly journals Identification of B-cell epitopes on the betanodavirus capsid protein

2007 ◽  
Vol 30 (7) ◽  
pp. 419-426 ◽  
Author(s):  
J Z Costa ◽  
A Adams ◽  
J E Bron ◽  
K D Thompson ◽  
W G Starkey ◽  
...  
Keyword(s):  
B Cell ◽  
Capsid Protein ◽  
B Cell Epitopes

Hierarchic T‐Cell Help to Non‐Linked B‐Cell Epitopes

1996 ◽  
Vol 44 (5) ◽  
pp. 478-484 ◽  
Author(s):  
N. H. C. BRONS ◽  
A. BLAICH ◽  
K.‐H. WIESMÜLLER ◽  
F. SCHNEIDER ◽  
G. JUNG ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
B Cell Epitopes ◽  
T Cell Help

scholarly journals 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

2004 ◽  
Vol 72 (12) ◽  
pp. 7360-7366 ◽  
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.

scholarly journals Accounting for B cell behaviour and sampling bias yields a superior predictor of anti-PD-L1 response in bladder cancer

2021 ◽  
Author(s):  
Ilya A Dyugay ◽  
Daniil K Lukyanov ◽  
Maria A Turchaninova ◽  
Andrew R Zaretsky ◽  
Oybek A Khalmurzaev ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Molecular Subtype ◽  
Specific Antigen ◽  
Therapy Response ◽  
Prognostic Indicator ◽  
Molecular Signature ◽  
Cell Functions

Tumor-infiltrating B cells and intratumorally-produced immunoglobulins (IG) play important roles in the tumor microenvironment and response to immunotherapy. IgG antibodies produced by intratumoral B cells may drive antibody-dependent cellular cytotoxicity (ADCC) and enhance antigen presentation by dendritic cells. Furthermore, B cells are efficient antigen-specific antigen presenters that can essentially modulate the behaviour of helper T cells. Here we investigated the role of intratumoral IG isotype and clonality in bladder cancer. Our results show that the IgG1/IgA ratio offers a strong and independent prognostic indicator for the Basal squamous molecular subtype and for the whole ImVigor210 cohort in anti-PD-L1 immunotherapy. Our findings also indicate that effector B cell functions, rather than clonally-produced antibodies, are involved in the antitumor response. High IgG1/IgA ratio was associated with relative abundance of cytotoxic genes and prominence of the IL-21/IL-21R axis suggesting importance of T cell/B cell interaction. We integrated the B, NK, and T cell components, employing immFocus-like normalization to account for the stochastic nature of tumor tissue sampling. Using a random forest model with nested cross-validation, we developed a tumor RNA-Seq-based predictor of anti-PD-L1 therapy response in muscle-invasive urothelial carcinoma. The resulting PRIMUS (PRedIctive MolecUlar Signature) predictor achieves superior sensitivity compared to PD-L1 expression scores or existing gene signatures, allowing for reliable identification of responders even within the desert patient subcohort analyzed as a hold out set.

Costimulation through the inducible costimulator ligand is essential for both T helper and B cell functions in T cell–dependent B cell responses

10.1038/ni947 ◽  
2003 ◽  
Vol 4 (8) ◽  
pp. 765-772 ◽  
Author(s):  
Tak W Mak ◽  
Arda Shahinian ◽  
Steve K Yoshinaga ◽  
Andrew Wakeham ◽  
Louis-Martin Boucher ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Helper ◽  
Cell Functions ◽  
Cell Responses ◽  
Inducible Costimulator ◽  
B Cell Responses

Viral fitness and antigenic determinants of porcine parvovirus at the amino acid level of the capsid protein

2021 ◽  
Author(s):  
André Felipe Streck ◽  
Cláudio Wageck Canal ◽  
Uwe Truyen
Keyword(s):  
Amino Acid ◽  
Capsid Protein ◽  
Immune Escape ◽  
Amino Acid Level ◽  
Binding Activity ◽  
Viral Fitness ◽  
Antigenic Determinants ◽  
Amino Acid Substitutions ◽  
Porcine Parvovirus ◽  
Predominant Factor

Since 2001, strains of porcine parvovirus (PPV), designated 27a -like strains, were observed in Europe, suggesting a predominance of these viruses over older strains. The reasons for the obvious evolutionary advantage are unknown. Here, a series of mutants containing amino acid replacements found in the predominant field strains were generated in a PPV-NADL2 background and their impact on replication efficiency and antibody binding activity was determined. Some amino acid substitutions observed in the 27a- like strains significantly increased viral fitness and decreased neutralization activity of sera raised against commercial vaccines and old virus strains (e.g. NADL2). These mutant viruses and a monoclonal antibody raised against a classical PPV strain defined an 27a-specific neutralizing epitope around amino acid 228 of the capsid protein VP2. Based on the analysis of the mutant viruses, it is hypothesized that the predominant factor for the global spread of the PPV-27a strain substitutions is an increased viral fitness of the 27a- like viruses, possibly supported by a partial immune selection. This is reminiscent to the evolution of canine parvovirus and worldwide replacement of the original virus by the so-called new antigenic types. Importance Porcine parvovirus is one of the most important causes of reproductive failure in swine. Recently, despite the continuous use of vaccines, “new” strains emerged, leading to the hypothesis that the emergence of new amino acid substitutions could be a viral adaptation to the immune response against the commercial vaccines. Our results indicate the amino acid substitutions observed in the 27a -like strains can modify viral fitness and antigenicity. However, an absolute immune escape was not evident.

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

Viruses ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 432 ◽  
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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