Rapid Generation of Medical Countermeasure Candidates Via Computational Variation Analysis

Abstract

Rapid responses to emerging infectious diseases are needed for viral and bacterial pathogens. For some pathogens, no medical countermeasures (MCMs) yet exist. Pathogen heterogeneity and antigenic variation lead to immune response escape mutations for some pathogens (e.g., influenza) limiting the effectiveness of medical countermeasures. High throughput sequencing enables characterization of large numbers of pathogen isolates to which residue variation analysis can be applied to identify low variability targets. Multiple approaches are proposed that leverage these low variability targets as the first step of medical countermeasure development. Classes of MCMs informed by this approach include the following: DNA or RNA vaccines, both B-cell and T-cell vaccination strategies, anti-viral RNA targeting, antibody therapeutics, and aptamer targeting of viral protein complex interfaces as potential treatment strategies for infected individuals. Variation analysis-designed countermeasures targeting the Ebola glycoprotein are presented to illustrate the concepts for the proposed multiple targeted countermeasures.