CE-BLAST makes it possible to compute antigenic similarity for newly emerging pathogens

Tianyi Qiu,Zhiwei Cao,Dingfeng Wu,Qingchen Zhang,Yang Huang,Jingxuan Qiu,Jianqing Xu,Chen Zhou,Xiaoyan Zhang,Tianlei Xu,Yiyan Yang,Kailin Tang,Han Xiao

doi:10.1038/s41467-018-04171-2

Tianyi Qiu, Zhiwei Cao + Show 11 more

Open Access

https://doi.org/10.1038/s41467-018-04171-2

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Abstract

Major challenges in vaccine development include rapidly selecting or designing immunogens for raising cross-protective immunity against different intra- or inter-subtypic pathogens, especially for the newly emerging varieties. Here we propose a computational method, Conformational Epitope (CE)-BLAST, for calculating the antigenic similarity among different pathogens with stable and high performance, which is independent of the prior binding-assay information, unlike the currently available models that heavily rely on the historical experimental data. Tool validation incorporates influenza-related experimental data sufficient for stability and reliability determination. Application to dengue-related data demonstrates high harmonization between the computed clusters and the experimental serological data, undetectable by classical grouping. CE-BLAST identifies the potential cross-reactive epitope between the recent zika pathogen and the dengue virus, precisely corroborated by experimental data. The high performance of the pathogens without the experimental binding data suggests the potential utility of CE-BLAST to rapidly design cross-protective vaccines or promptly determine the efficacy of the currently marketed vaccine against emerging pathogens, which are the critical factors for containing emerging disease outbreaks.

Highlights

Major challenges in vaccine development include rapidly selecting or designing immunogens for raising cross-protective immunity against different intra- or inter-subtypic pathogens, especially for the newly emerging varieties
For each input antigen with the structure information, the conformational epitope will be translated into a series of fingerprints and compared with the predefined or user-uploaded datasets through Conformational Epitope (CE)-BLAST, a list of hit-epitope structures with predicted similarity scores will be provided in descending order as output
A web server has been constructed with built-in epitope libraries containing simulated structure databases of the HA antigen for influenza virus (A/H1N1 & A/ H3N2), Envelope (E) antigen for dengue viruses (DENV) and ZIKV, and known conformational epitopes derived from the Protein Databank (PDB) immune complex

Summary

Introduction

Major challenges in vaccine development include rapidly selecting or designing immunogens for raising cross-protective immunity against different intra- or inter-subtypic pathogens, especially for the newly emerging varieties. We propose a computational method, Conformational Epitope (CE)-BLAST, for calculating the antigenic similarity among different pathogens with stable and high performance, which is independent of the prior binding-assay information, unlike the currently available models that heavily rely on the historical experimental data. The ability of CE-BLAST to detect the antigenic variance is rigorously evaluated using different sets of immune-assay data on both intra- and inter-subtypic pathogens, as well as cross-virus cases. It is initially tested with intra-subtypic pathogen data of influenza A/H3N2 antigen including 3867 historical HI assays, and combined with the experimental validation on a new antigen of A/H3N2. The web server of CE-BLAST can be accessed at http://badd.tongji.edu.cn/ce_blast/ or http://bidd2. nus.edu.sg/czw/ce_blast/

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