October 19, 2022

In The News: For Decades, Fear and Failure in the Hunt for an RSV Vaccine. Now, Success.

The Washington Post reports on the “renaissance” of respiratory syncytial virus vaccine development following its catastrophic beginnings in the 1960s. Included in those ill-fated beginnings were a pair of infant deaths that fomented hesitation to pursue and test an inactivated lab vaccine candidate in young children. That began to change with the option to use a less direct route to providing protection through antibodies and a chance pairing of NIH researchers.

Those researchers were recruited to work on HIV for NIH. HIV was well-funded, whereas RSV was “nuisance without a name” that did not attract attention or funding. However, one joined only if he could also continue working on RSV and convinced his new lab-mate to do so, as well. The latter had learned to use X-ray crystallography, which reveals proteins at an atomic level, and would prove critical to their work once they looked at maternal antibodies.

Developing a vaccine based on antibodies passed from mother to child during pregnancy opened a new route to immunization. Antibody drugs mimicking maternal immunity could create a potent candidate. The issue then became RSV’s molecular surface. Its F protein structure could shift before binding to a cell. Using X-ray crystallography, researchers could determine its precise ‘lollipop’ shape before it transformed to ‘golf tee’ shape upon entering cells.

To build a vaccine, scientists looked to train the immune response to target the lollipop. Doing so required an F protein frozen into that shape. Researchers sculpted 150 candidates and chose the best one. They found it provoked a powerful protective response in lab mice and monkeys. The researchers then looked to the pharmaceutical industry to take the vaccine to trial.

Thanks to these advancements, pharmaceutical giants are competing to control a potential multibillion-dollar market on a virus that causes 58,000 hospitalizations each year of children under five in the United States alone. Two RSV vaccines (one developed by GSK and another by Pfizer) have shown to provide protection in large-scale adult trials. Meanwhile, AstraZeneca and Sanofi have developed long-lasting protection in a major trial through a preventative injection of monoclonal antibodies. The long-term goal is to take the process and apply it to other diseases.

PIDS members Octavio Ramilo, Flor Muñoz, and William Gruber appear in the article. On the vaccine mimicking maternal protection, Muñoz said, “Giving a vaccine to pregnant women is mimicking an actual process: Moms who have had RSV are boosted…and those babies will have higher immunity at birth and lower risk of getting infected in the first few months of life.” And Ramilo added, “After all these years…it’s a very exciting time for us.”

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