Structure-based design and development of next generation Respiratory Syncytial Virus (RSV) vaccine

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are prevalent respiratory pathogen that primarily affect infants, young children, older adults, and individuals with compromised immune systems. Current RSV subunit vaccines are based on a fusion protein that is stabilized in the prefusion conformation and linked to a heterologous foldon trimerization domain to obtain a prefusion F (preF) trimer. Previous research had shown that current RSV vaccines induce undesirable antibodies in non-human primates, mice and humans. To overcome this, we designed foldon-free RSV and MPV preF trimers by adding endogenous trimerization domains, introducing disulfide bonds between monomers and negate hotspots of charge repulsion. The highly stable prefusion conformation was validated using antigenic and electron microscopy analysis. The preF is immunogenic and protective, boosts high neutralizing antibody titers in mice and non-human primates against both RSV and hMPV. The stable preF demonstrates enhanced stability under both refrigerated and elevated temperature conditions. The stable preF design is a promising option as a foldon-independent candidate for a next-generation RSV and hMPV vaccine.

Dr. Lei Chen, Founder and CEO of Yikang Biotech, received his Ph.D. from Osaka University, Japan. He served as a Senior Staff Scientist at NIH/NIAID/VRC for over a decade, specializing in vaccine R&D for RSV, HIV, and SARS. He was a key contributor to the world's first structurebased RSV vaccine (DS-Cav1). Dr. Chen holds over 30 patents and has published 45 SCI papers, including 7 in Science and Cell. He is currently leading next-generation RSV vaccine development at Yikang Biotech, with advantages over GSK's AREXVY and Pfizer's ABRYSVO.