Landscape of neutralizing assessment of monoclonal antibodies against dengue virus

Abstract

The majority of antibody binding sites (B-cell epitopes) on antigens are discontinuous. The binding between antigen and antibody is specific, but in some cases, the antibody elicited by one antigen will show cross-reactivity against other antigens. We have developed a bioinformatics-based approach for the analysis of sequence variability of neutralizing antibody binding sites and the assessment of coverage by individual neutralizing antibodies. The antigenic analysis of functional sites on the envelope (E) protein from dengue virus has been used as a case study. The description of B-cell epitopes, measurement of epitope similarity among different strains, and estimation of antibody neutralizing coverage provide insights in antibody cross-reactivity. We have defined a generalized method for the analysis of cross-reactivity of neutralizing antibodies that is also applicable to the analysis of other pathogens. This method adds to the toolset available for the characterization and the design of broadly neutralizing vaccines.

Big Data Analytics in Immunology: A Knowledge-Based Approach

“…We developed a generic method for the assessment of neutralizing properties of monoclonal antibodies. Previously, dengue virus was used to demonstrate a generalized method [ 27 ]. This methodology has direct relevance to the characterization and the design of broadly neutralizing vaccines.…”

“…In TANTIGEN and HPVdB, a T-cell epitope visualization tool has been implemented to display epitopes in all isoforms of a tumor antigen or sequences of a HPV genotype. The B-cell visualization tool in FLAVIdB and FLUKB displays neutralizing B-cell epitope positions on viral protein three-dimensional (3D) structures [ 26 , 27 ]. To analyze viral sequence variability, given a MSA of a set of sequences, a tool was developed to calculate Shannon entropy at each alignment position.…”

A systematic analysis of a broadly neutralizing antibody AR3C epitopes on Hepatitis C virus E2 envelope glycoprotein and their cross-reactivity

“…A total of 589 different patterns of discontinuous peptides on F10 B-cell epitope were extracted from 45,812 HA sequences. The mAb 2H12 [ 32 ] is a broadly neutralizing antibody shown to neutralize serotypes DENV1, 3 and 4, has 57 different patterns of discontinuous peptides on B-cell epitope that cover 4,659 dengue E protein sequences in dengue dataset [ 33 ]. In the current study, 5340 E protein sequences from HCV, which is a similar sequence set size as in dengue viruses, generated almost an order of magnitude larger diversity: 402 different discontinuous peptides at the mAb AR3C binding site have been identified.…”