Amsterdam institute for Immunology and Infectious diseases

In 2007, a breakthrough in respiratory medicine was made in Amsterdam. Prof. Hergen Spits and his team, working at the AMC and the start-up AIMM Therapeutics, isolated a potent antibody, D25, from a single immune cell of a Dutch blood donor. This antibody targeted the respiratory syncytial virus (RSV), a common cold virus that poses a serious threat to infants. Today, its optimized successor, nirsevimab, is part of the national immunization program, preventing thousands of hospitalizations each year in the Netherlands and beyond. We spoke with Prof. Spits, member of the Amsterdam institute for Immunology and Infectious diseases, about the scientific journey behind this breakthrough, the challenges of translating discovery into global impact, and the lessons for a new generation of immunologists.

RSV is a virus that causes mild symptoms in adults but can lead to severe illness in infants, with 1.5–2% of infected babies requiring hospitalization and some needing intensive care. Traditional vaccination is not effective in very young infants due to their immature immune systems. Prof. Spits and his team set out to find antibodies from adults who had successfully fought off RSV, hoping to use these as a protective therapy for babies.

Using innovative technology to isolate monoclonal antibodies from human B cells, the team discovered D25, which could neutralize RSV in laboratory tests. The antibody specifically targeted the F-protein, a key molecule involved in the virus’s ability to infect lung cells. This discovery was the result of a crucial decision: to screen for functional neutralization rather than simple binding, a choice informed by earlier experiences with generating monoclonal antibodies against human immune cells.

A surprising discovery in the lab

The journey from initial discovery to understanding the mechanism of action was full of unexpected twists. After isolating the antibody, the team was surprised to find that, contrary to their expectations, it did not bind to inactivated RSV in standard laboratory tests. Only later did they realize that the antibody specifically recognized the F-protein in its native, active form on live virus particles, a protein essential for the virus to fuse with and infect lung cells. This insight revealed a unique structural change in the F-protein during the infection process, which the antibody could target.

Prof. Hergen Spits reflects: ‘We were surprised to see that our antibody didn’t bind to the inactivated virus, but only to the live virus. This led colleagues at the National Institute of Health in the US to uncover a crucial mechanism, our antibody targets the F-protein in its active state, which is key for the virus to infect cells. That was a real breakthrough in understanding how to neutralize RSV.’

From discovery to clinical application

After demonstrating the antibody’s effectiveness, the team partnered with MedImmune (now part of AstraZeneca) to further develop and optimize D25. Improvements included extending the antibody’s half-life to provide protection throughout the RSV season and increasing its binding affinity. Clinical trials confirmed that the optimized antibody, nirsevimab, was safe and highly effective, reducing hospitalizations for RSV by approximately 80%.

Nirsevimab was approved in Europe (2022) and in the United States (2023), where it was quickly adopted into the national vaccination program. In the Netherlands, implementation required careful coordination among health authorities, including the RIVM, to ensure that all infants, including those born at home, could receive the antibody.

Innovation and collaboration

The success of nirsevimab highlights the value of fundamental immunological research and the importance of collaboration between academia and industry. The technology developed at AIMM and AMC enabled the isolation of highly effective antibodies, not only against RSV but also other viruses. The partnership with AstraZeneca ensured that the discovery could be translated into a product with global health impact.

Lessons for the next generation

Prof. Spits emphasizes that scientific breakthroughs require both insight and a measure of luck. The decision to focus on functional assays was essential, and the journey from laboratory discovery to clinical application involved overcoming scientific, financial, and regulatory challenges. For young immunologists, the story of D25 and nirsevimab demonstrates the importance of perseverance, collaboration, and the willingness to pursue innovative approaches.

A lasting impact

The introduction of nirsevimab has already led to a significant reduction in RSV-related hospitalizations in the Netherlands in 2025.

This Dutch discovery, rooted in fundamental science and realized through collaboration, now protects infants worldwide, an achievement that underscores the power of translational immunology and the impact of research at AI&I.

Text: Hergen Spits and Esmée Vesseur