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Hanover, Germany, May 27, 2025 — A new study has shed light on why monoclonal antibody treatments, once hailed as a breakthrough in fighting COVID-19, are often outmaneuvered by rapidly mutating viruses—and how a nature-inspired solution could restore their effectiveness.
Researchers from TWINCORE, in collaboration with teams from Hanover and Bern, have revealed the “Achilles’ heel” of monoclonal antibodies: their vulnerability to single-point mutations in viruses. The findings, published in eBioMedicine, could have far-reaching implications for the future of antiviral therapies.
The Problem: Viruses Evolve, Antibodies Fall Behind
Monoclonal antibodies are lab-engineered proteins designed to target a specific part of a virus. During the pandemic, several such treatments were developed to neutralize SARS-CoV-2, the virus behind COVID-19. However, as Dr. Matthias Bruhn, lead author and postdoctoral researcher at TWINCORE, explains, “A single mutation in the virus can be enough for an antibody to lose its effectiveness.”
This phenomenon was observed in animal studies conducted with the University of Veterinary Medicine Hannover Foundation. While most hamsters treated with the new antibodies were protected, a few still fell ill. Genetic analysis revealed that these animals had been infected by viruses carrying a single mutation—one that allowed the virus to evade the antibody’s attack.
The Solution: Mimicking Nature’s Diversity
Unlike monoclonal antibodies, our natural immune system produces a diverse mix of antibodies, known as polyclonal antibodies, which target multiple sites on a virus. Inspired by this, the research team tested a combination approach: using two or three different monoclonal antibodies at once.
“We copied the recipe for this strategy directly from nature,” says Bruhn. By targeting the virus at several points simultaneously, the chances of a single mutation allowing escape are drastically reduced.
International Collaboration Drives Innovation
The research was made possible by a network of national and international partners, including the Hanover Medical School and the Swiss Institute of Virology and Immunology. Prof. Ulrich Kalinke, Executive Director of TWINCORE, highlighted the importance of collaborative efforts: “This networking is made possible by alliances such as the RESIST Cluster of Excellence and DZIF, the German Center for Infection Research.”
What’s Next?
The study’s findings may prompt a shift in how monoclonal antibody therapies are designed—not just for COVID-19, but for a range of viral diseases. By embracing combinations that mimic the body’s own immune diversity, scientists hope to stay one step ahead of viral evolution.
Disclaimer:
This article is based on preliminary research findings published in eBioMedicine and summarized from a news release on Medical Xpress (https://medicalxpress.com/news/2025-05-antibodies-achilles-heel-viruses-immune.html). The research is ongoing, and while promising, the proposed strategies have not yet been widely adopted in clinical practice. Readers should consult healthcare professionals for medical advice and stay updated with guidance from health authorities.
