Breakthrough in RSV Protein Stabilization: Paving the Way for Improved Vaccines

In most cases, respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause mild cold-like symptoms. However, they can lead to severe pneumonia or death in infants and seniors.

Scripps Research scientists have made progress in developing vaccines for these viruses. Their study, published in Nature Communications on November 16, 2024, focuses on the structure and stability of a key protein from both viruses. Their findings indicate that new RSV vaccines may be more effective than current options, and they aim to create a vaccine for hMPV, which currently has no available commercial vaccine.

Jiang Zhu, the study’s senior author, emphasizes that combining vaccines for RSV and hMPV could significantly lower hospitalizations among vulnerable populations during flu season.

Zhu highlights the fragility of the pre-fusion F protein, which cannot be used directly in vaccines because its structure changes too rapidly. A post-fusion protein does not prepare the immune system effectively against the virus. He investigates how to stabilize the pre-fusion protein to enhance vaccine development.

The research team analyzed F proteins from four existing RSV vaccines: Arexvy, mResvia, Abrysvo, and an experimental one. They found that some pre-fusion proteins were unstable and converted to less effective forms. Structural analysis showed an “acidic patch” in the protein that caused instability.

Zhu reengineered the RSV F protein by changing molecules in its center to stabilize it. This new protein was more stable in lab tests and successfully vaccinated mice against RSV.

For the hMPV F protein, Zhu used a strong chemical bond to enhance stability. The modified protein proved stable enough to be considered for vaccine development.

The study concludes that similar approaches could be applied to other viral proteins, potentially improving vaccine design.

Authors of the study include Yi-Zong Lee, Jerome Han, Yi-Nan Zhang, Garrett Ward, Keegan Braz Gomes, Sarah Auclair, Robyn L. Stanfield, Linling He, and Ian A. Wilson from Scripps Research.

The research received funding from Uvax Bio, a company spun off from Scripps Research focused on developing vaccines for infectious diseases.