Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - Antibodyomics (Vaccine profiling and immunodiagnostic discovery by high-throughput antibody repertoire analysis)

Teaser

Vaccines and immunodiagnostics have been vital for public health and medicine, however a quantitative molecular understanding of vaccine-induced antibody responses is lacking. Antibody research is currently going through a big-data driven revolution, largely due to progress in...

Summary

Vaccines and immunodiagnostics have been vital for public health and medicine, however a quantitative molecular understanding of vaccine-induced antibody responses is lacking. Antibody research is currently going through a big-data driven revolution, largely due to progress in nextgeneration
sequencing (NGS) and bioinformatic analysis of antibody repertoires. A main advantage of high-throughput antibody repertoire analysis is that it provides a wealth of quantitative information not possible with other classical methods of antibody analysis (i.e., serum titers) The overall goal of this proposal will be to apply high-throughput antibody repertoire analysis for quantitative vaccine profiling and discovery of next-generation immunodiagnostics. Using mouse subunit vaccination as our model system, we will answer for the first time, a fundamental biological question within the context of antibody responses - what is the link between genotype (antibody repertoire) and phenotype (serum antibodies)? We will expand upon this approach for improved rational vaccine design by quantitatively determining the impact of a comprehensive set of subunit vaccination parameters on complete antibody landscapes.Finally, we will develop advanced bioinformatic methods to discover immunodiagnostics based on antibody repertoire sequences. In summary, this proposal lays the foundation for fundamentally new approaches in the quantitative analysis of antibody responses, which long-term will promote the development of next-generation vaccines and immunodiagnostics.

Work performed

Thus far a large set of foundational work for the project has been achieved. Much of the experimental work related to mouse immunizations has been completed and a major fraction of the sequencing experiments are also completed. Ongoing work includes data analysis, additional sequencing, and development of advanced bioinformatic tools. To date several publications have accepted in peer-reviewed journals that describe advancements in the computational and bioinformatic methods of antibody repertoires and potential for antibody sequencing to support antibody discovery.

Final results

We have developed advanced machine learning and deep learning tools which are helping to uncover high-dimensional sequence properties that are able to predict functionality of antibodies. This is a major development and lays the foundation for using antibody sequencing as a powerful tool for immunodiagnostics, vaccine development, and antibody engineering. One publication is completed, another two are in preparation, and a patent application is in preparation.