Innovative Breakthrough Advances RSV Prevention

MEDICINE | In 2022, about one in every 500 babies ages six months and younger was hospitalized due to respiratory syncytial virus (RSV), the second leading cause of infant mortality in the U.S. But thanks to the contributions of Larner College of Medicine researcher Sean Diehl, Ph.D.’03, associate professor of microbiology and molecular genetics, and colleagues, this may soon no longer be the case.

In 2010, Diehl, alongside researchers at Amsterdam University Medical Centers (UMC), made a breakthrough — they found an antibody that offers protection against this life-threatening virus for newborns. After over a decade of tinkering and testing, the U.S. Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC), alongside the Advisory Committee on Immunization Practices (ACIP), this summer unanimously approved to recommend that the antibody drug, known as Beyfortus (nirsevimab) and dispensed through Sanofi and AstraZeneca, be incorporated into the vaccination schedule for infants under eight months of age.

RSV is a virus that can cause acute respiratory infections in people of all ages. While the majority of infants and young children may exhibit minor cold-like symptoms from RSV, certain babies, particularly during their initial infection, can encounter more severe lower respiratory tract ailments, such as pneumonia and bronchiolitis. Premature infants and those with chronic lung conditions or notable congenital heart problems are at the greatest susceptibility to severe RSV disease.

Beyfortus stands apart as a passive immunization, delivering a single dose of a long-acting monoclonal antibody that blocks RSV’s ability to infect cells. This unique approach offers timely and direct protection against disease without requiring the activation of the immune system in the ways that traditional active immunizations or vaccines do. And research has also shown that Beyfortus additionally allows a baby’s immune system to generate its own protective responses to RSV.

Behind the development of Beyfortus were two decades of work that began in 2003 in Amsterdam while Diehl was a postdoctoral fellow at Amsterdam UMC. Working with immunologist and professor of cell biology Hergen Spits, Ph.D., Diehl invented a technique—one that involved mimicking the activation process of human immune system B cells while lengthening their lifespan—that was later applied to the RSV prevention efforts.

Human B cells serve as formidable defenders, producing antibodies that shield individuals from infections like RSV, but unleashing their full potential for potent RSV antibodies has proven to be a challenging task. Diehl and his colleagues embarked on a groundbreaking journey to comprehend the intricate workings of B cells, which ultimately allowed them to replicate the activation process in the lab. This work led to a transformative discovery of four potent RSV antibodies. These antibodies held the promise of revolutionizing prevention and treatment strategies for this respiratory virus.

Discovery of potent RSV antibodies marked a pivotal advancement in the fight against RSV. This summer, Beyfortus received its final FDA and CDC approval.

The impact of this research can extend beyond RSV, to development of antibodies against other infectious diseases, including monoclonal antibody therapies for dengue, Zika, and norovirus. Monoclonal therapies for COVID-19 also gained momentum during the pandemic. Importantly, Beyfortus is approved for all infants and has been included in the CDC’s Vaccines for Children program for the winter 2023 RSV season.