One of the most demanding and critical challenges of developing an effective new vaccine is selecting the element of the pathogen that the vaccine will target. If one chooses a target that isn’t appropriately accessible to the immune system then immune system cells won’t properly identify the pathogen to fight it.  If instead one chooses a target that gets mutated rapidly, the vaccine will quickly lose effectiveness.  Therefore, identifying an appropriate target is of utmost importance for the effectiveness and value of the vaccine.

Since the late 1970s, DNA sequencing has been a mainstay of biological research to study viruses and living systems. It enables comparing a sequence of DNA obtained from a test to a reference in order to learn about the organism it came from. This approach has become fundamental to drug and vaccine development. 

Photo: It was a pleasure to contribute to the novel research of Dr. Tim Keys at the Institute for Microbiology at the ETHZ, and we look forward to future collaborations. Left: Dr. Tim Keys, Right: Dr. Dan Bower, QuadraticMed CTO.

QuadraticMed were tasked with the challenge of developing a reusable method to enable identification of high-yield targets for next-generation vaccine development. Working with protected, proprietary research and sequencing data, we developed a highly accurate, automated workflow that handles the variability of genetic data to classify and quantify data according to specific criteria.  In-house researchers now have a method they can use for target selection for current and future projects as their database of data grows. Using this tool, the valuable data they are generating in the laboratory can be searched and mined to better understand the defences and evolution of the pathogen and guide successful vaccine development.

Additionally, the tool serves an essential role to track mutational changes of the pathogen as the pathogen evolves in different environments or to evade the host’s immune system.  Identifying features of the pathogen that are highly variable or subject to rapid change over time enable development of vaccines against more stable, conserved targets which will remain effective for longer.  

Being able to track mutational changes also provides critical information regarding the emergence of new variants of a pathogen and the lethality and infectivity of those new variants.  The urgency of this information has become clear from recent pandemics, including COVID-19, Ebola, H1N1 influenza, and SARS.  Our ability to respond rapidly to pathogens that emerge in the future depends on having the tools in place to quickly rank potential vaccine targets and track the evolution of the pathogens.