An integrated in silico immuno-genetic analytical platform provides insights into COVID-19 serological and vaccine targets

Abstract

BackgroundThe COVID-19 pandemic, caused by the SARS-CoV-2 virus, has a major global health and socio-economic burden. It has instigated the mobilisation of resources into the development of control tools, such as diagnostics and vaccines. The poor performance of some diagnostic serological tools has emphasised the need for up to date immune-informatic analyses to inform the selection of viable targets for further study. This requires the integration and analysis of genetic and immunological data for SARS-CoV-2 and its homology with other human coronavirus species to understand cross-reactivity. MethodsWe have developed an online "immuno-analytics" resource to facilitate SARS-CoV-2 research, combining an extensive B/T-cell epitope mapping and prediction meta-analysis, and human CoV sequence homology mapping and protein database annotation, with an updated variant database and geospatial tracking for >7,800 non-synonymous mutation positions derived from >150,000 whole genome sequences. To demonstrate its utility, we present an integrated analysis of SARS-CoV-2 spike and nucleocapsid proteins, both being vaccine and serological diagnostic targets, including an analysis of changes in relevant mutation frequencies over time. ResultsOur analysis reveals that the nucleocapsid protein in its native form appears to be a sub-optimal target for use in serological diagnostic platforms. The most frequent mutations were the spike protein D614G and nsp12 L314P, which were common (>86%) across all the geographical regions. Some mutations in the spike protein (e.g. A222V and L18F) have increased in frequency in Europe during the latter half of 2020, detected using our automated algorithms. The tool also suggests that orf3a proteins may be a suitable alternative target for diagnostic serologic assays in a post-vaccine surveillance setting. ConclusionsThe immuno-analytics tool can be accessed online (http://genomics.lshtm.ac.uk/immuno) and will serve as a useful resource for biological discovery and surveillance in the fight against SARS-CoV-2. Further, the tool may be adapted to inform on biological targets in future outbreaks, including potential emerging human coronaviruses that spill over from animal hosts.