Selection of Cryptic B-Cell Epitopes Using Informational Analysis of Protein Sequenses

Abstract

Sub-unit vaccines are synthetic or recombinant peptides representing T- or B-cell epitopes of major protein antigens from a particular pathogen. Epitope selection requires the synthesis of peptides that overlap the protein sequences and screening for the most effective ones. In this study a new method of immunogenic peptide selection based on the analysis of information structure of protein sequences is suggested. The analysis of known B-cell epitope location in the information structure of Aspergillus fumigatus proteins Asp f 2 and Asp f 3 has shown that epitopes are scattered along the sequences of proteins for the exception of sites with Increased Degree Information Coordination (IDIC). Based on these results peptides from different allergens such as Asp f 2, Der p 1, and Fel d 1 were selected and produced in a recombinant form in the context of yeast virus-like particles (VLPs). Immunization of mice with VLPs containing peptides form allergens has induced the production of IgG able to recognize full-length antigens. This result suggests that the analysis of information structure of proteins can be used for the selection of peptides possessing cryptic B-cell epitope activity.

Entropy Analysis of Protein Sequences Reveals a Hierarchical Organization

“…The flexibility of one of the interacting protein chains ensures efficient interaction between amino acid residues at the interface. The choice of sites containing positively charged amino acid residues Arg and Lys of ADD+ sites as B-epitopes increases their immunogenicity several times, which can be used in the development of vaccines [ 11 , 12 ]. An analysis of the location of ADD+ and ADD− sites in the spatial structure of proteins made it possible to propose a model for the functioning of hem-containing proteins [ 13 ].…”

All the small things: How virus‐like particles and liposomes modulate allergic immune responses

“…Using that strategy, Harris and Hirschberg were able to induce allergen‐specific CD4 + T cell responses, which were Der p 1 111–139 peptide specific and abrogated allergen‐specific IL‐5 secretion upon restimulation with Der p 1 peptide. In a similar vein, conjugation of the major T cell epitope of the Aspergillus fumigatus allergen Asp f to yeast p1 protein, known for its spontaneous assembly into VNP , downregulated both, allergen‐specific T cell responses and allergen‐specific serum IgE, IgG 2a , and Ig G3 , but not IgG 1 and IgG 2b levels . A slightly different approach was taken by Leb et al., who decorated MoMLV‐based VNP with HLA class II molecules already displaying the immunodominant epitope of the major mugwort pollen allergen Art v 1 in the presence or absence of distinct co‐stimulatory molecules .…”