Identification of a conserved linear B-cell epitope in the Staphylococcus aureus GapC protein

Wang, Mengyao; Wei, Yuhua; Yu, Weiwu; Wang, Lizi; Zhai, Lu; Li, Xiaoting; Wang, Xintong; Zhang, Hua; Feng, Zhenyue; Yu, Liquan; Yu, Yao; Ma, Jingyun; Cui, Yudong

doi:10.1016/j.micpath.2018.03.007

Cited by 7 publications

(4 citation statements)

References 37 publications

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“…[126,127]. The use of phage display libraries to characterize immune responses in studies of vaccines [128,129,130,131] allergy [121,127,132] and autoimmunity [133] is highly analogous to profiling of alloimmune responses to a biotherapeutic. Phage display methodology is continually evolving and improving, particularly by incorporating additional techniques including bioinformatics and structural analysis for quality control [121,127,134,135,136] and to identify clusters of surface-exposed side chains on protein antigens that recapitulate the patterns/properties of the phage-displayed proteins (e.g., scFvs) or peptides [133].…”

Section: Identifying and Modifying B-cell Epitopes In Biotherapeuticsmentioning

confidence: 99%

Anti-Drug Antibodies: Emerging Approaches to Predict, Reduce or Reverse Biotherapeutic Immunogenicity

Pratt

2018

Antibodies

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Abstract:The development of anti-drug antibodies (ADAs) following administration of biotherapeutics to patients is a vexing problem that is attracting increasing attention from pharmaceutical and biotechnology companies. This serious clinical problem is also spawning creative research into novel approaches to predict, avoid, and in some cases even reverse such deleterious immune responses. CD4 + T cells are essential players in the development of most ADAs, while memory B-cell and long-lived plasma cells amplify and maintain these responses. This review summarizes methods to predict and experimentally identify T-cell and B-cell epitopes in therapeutic proteins, with a particular focus on blood coagulation factor VIII (FVIII), whose immunogenicity is clinically significant and is the subject of intensive current research. Methods to phenotype ADA responses in humans are described, including T-cell stimulation assays, and both established and novel approaches to determine the titers, epitopes and isotypes of the ADAs themselves. Although rational protein engineering can reduce the immunogenicity of many biotherapeutics, complementary, novel approaches to induce specific tolerance, especially during initial exposures, are expected to play significant roles in future efforts to reduce or reverse these unwanted immune responses.

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Section: Identifying and Modifying B-cell Epitopes In Biotherapeuticsmentioning

confidence: 99%

Anti-Drug Antibodies: Emerging Approaches to Predict, Reduce or Reverse Biotherapeutic Immunogenicity

Pratt

2018

Antibodies

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“…To identify amino acids that are critical for the epitope, each residue was sequentially substituted with alanine as described previously [23][24][25]. The primers used to introduce the specific mutations are shown in Table S2.…”

Section: Site-directed Mutagenesis Assaymentioning

confidence: 99%

Identification of a B-Cell Epitope in the VP3 Protein of Senecavirus A

Chen

Wang

et al. 2021

Viruses

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Senecavirus A (SVA) is a member of the genus Senecavirus of the family Picornaviridae. SVA-associated vesicular disease (SAVD) outbreaks have been extensively reported since 2014–2015. Characteristic symptoms include vesicular lesions on the snout and feet as well as lameness in adult pigs and even death in piglets. The capsid protein VP3, a structural protein of SVA, is involved in viral replication and genome packaging. Here, we developed and characterized a mouse monoclonal antibody (mAb) 3E9 against VP3. A motif 192GWFSLHKLTK201 was identified as the linear B-cell epitope recognized by mAb 3E9 by using a panel of GFP-tagged epitope polypeptides. Sequence alignments show that 192GWFSLHKLTK201 was highly conserved in all SVA strains. Subsequently, alanine (A)-scanning mutagenesis indicated that W193, F194, L196, and H197 were the critical residues recognized by mAb 3E9. Further investigation with indirect immunofluorescence assay indicated that the VP3 protein was present in the cytoplasm during SVA replication. In addition, the mAb 3E9 specifically immunoprecipitated the VP3 protein from SVA-infected cells. Taken together, our results indicate that mAb 3E9 could be a powerful tool to work on the function of the VP3 protein during virus infection.

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“…GAPDH, as a key enzyme in the glycolytic pathway, is a surface protein of S. iniae . It reversibly catalyzes the oxidative phosphorylation of glyceral-dehyde-3-phosphate into 1,3 bisphosphoglycerate and is associated with protein binding, cell signaling in many organisms, and immune evasion in bacteria [ 31 , 32 , 33 ], while PDHA1 is a phosphorylated protein involved not only in microbial biochemical metabolism but also in pathogenicity. For example, PDHA1 inhibitors have been reported to kill E. coli in vitro, and a synthetic inhibitor has been reported to kill both fungi and bacteria [ 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

Development and Evaluation of Recombinant B-Cell Multi-Epitopes of PDHA1 and GAPDH as Subunit Vaccines against Streptococcus iniae Infection in Flounder (Paralichthys olivaceus)

et al. 2023

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Streptococcus iniae is a severe Gram-positive pathogen that can infect a wide range of freshwater and marine fish species. In continuation of our earlier studies on the development of S. iniae vaccine candidates, pyruvate dehydrogenase E1 subunit alpha (PDHA1) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were highly efficacious in protecting flounder (Paralichthys olivaceus) against S. iniae. In the present study, to investigate the potential of multi-epitope vaccination strategy to prevent flounder against S. iniae infection, the liner B-cell epitopes of PDHA1 and GAPDH proteins were predicted using a bioinformatics approach and were identified by immunoassay, and recombinant B-cell multi-epitopes of PDHA1 and GAPDH (rMEPIP and rMEPIG) containing immunodominant epitope-concentrated domains were expressed in Escherichia coli BL21 (DE3) and were used as a subunit vaccine to immunize healthy flounder, while recombinant PDHA1 (rPDHA1), GAPDH (rGAPDH) and formalin-inactivated S. iniae (FKC) served as controls. Then, the immunoprotection efficacy of rMEPIP and rMEPIG was evaluated by determining the percentages of CD4-1+, CD4-2+, CD8β+ T lymphocytes and surface-IgM-positive (sIgM+) lymphocytes in peripheral blood leucocytes (PBLs), spleen leucocytes (SPLs) and head kidney leucocytes (HKLs), as well as total IgM, specific IgM, and relative percentage survival (RPS) post immunization, respectively. It was found that fish immunized with rPDHA1, rGAPDH, rMEPIP, rMEPIG and FKC showed significant increases in sIgM+, CD4-1+, CD4-2+, and CD8β+ lymphocytes and production of total IgM and specific IgM against S. iniae or recombinant proteins rPDHA1 and rGAPDH, which indicated the activation of humoral and cellular immune responses after vaccination. Moreover, RPS rate of the multi-epitope vaccine rMEPIP and rMEPIG groups reached 74.07% and 77.78%, higher than that of rPDHA1 and rGAPDH (62.96% and 66.67%) and KFC (48.15%). These results demonstrated that B-cell multi-epitope protein vaccination, rMEPIP and rMEPIG, could give a better protective effect against S. iniae infection, which provided a promising strategy to design the efficient vaccine in teleost fish.

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Identification of a conserved linear B-cell epitope in the Staphylococcus aureus GapC protein

Cited by 7 publications

References 37 publications

Anti-Drug Antibodies: Emerging Approaches to Predict, Reduce or Reverse Biotherapeutic Immunogenicity

Anti-Drug Antibodies: Emerging Approaches to Predict, Reduce or Reverse Biotherapeutic Immunogenicity

Identification of a B-Cell Epitope in the VP3 Protein of Senecavirus A

Development and Evaluation of Recombinant B-Cell Multi-Epitopes of PDHA1 and GAPDH as Subunit Vaccines against Streptococcus iniae Infection in Flounder (Paralichthys olivaceus)

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