New Method Accelerates Identification of Mutations Responsible for Immune Escape

Researchers at the Helmholtz Centre for Infection Research have developed a novel approach to identify key mutations responsible for viral immune escape. The method, called reverse mutational scanning, offers a more precise way to analyze virus variants and could accelerate vaccine development against evolving pathogens.

The team, led by Luka Cicin-Sain, modified the existing mutational scanning technique to better understand how viruses like SARS-CoV-2 evade immune recognition. Instead of introducing mutations from a new variant into the original virus, they reversed individual mutations in the new variant back to the original form.

Najat Bdeir, first author of the study published in Nature Communications, explained their process using SARS-CoV-2 as an example: "To find out which mutations are responsible for the immune escape of this virus variant, we created various pseudoviruses in which one of the 33 different mutations was reversed, in the direction of the original virus BA.2."

The researchers tested these pseudoviruses against blood samples from healthcare workers vaccinated with an Omicron XBB.1.5-effective vaccine. This approach allowed them to identify three specific mutations in the spike protein responsible for immune escape. 

Prof. Cicin-Sain emphasized the importance of this reverse approach: "If we start from the original variant and insert a mutation in an area that is actually recognized by antibodies, there is a high probability that antibodies binding to another part of the virus will still recognize and neutralize the virus. The actual contribution of the mutation to immune escape cannot be adequately detected in this way."

The team believes this method could be applied to other viruses and potentially train AI models to predict immune-escaping mutations. "If we could produce vaccines based on pre-adapted vaccines, we would be faster than the virus!" Cicin-Sain added, highlighting the potential for more rapid vaccine development in response to emerging virus variants.