Title : Structure-based design and development of next-generation Respiratory Syncytial Virus (RSV) vaccine
Abstract:
Respiratory syncy????al 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 conforma????on and linked to a heterologous foldon trimeriza????on domain to obtain a prefusion F (preF) trimer. Previous research had shown that current RSV vaccines induce undesirable an????bodies in non-human primates, mice and humans. To overcome this, we designed foldon-free RSV and MPV preF trimers by adding endogenous trimeriza????on domains, introducing disulfide bonds between monomers and negate hotspots of charge repulsion. The highly stable prefusion conforma????on was validated using an????genic and electron microscopy analysis. The preF is immunogenic and protec????ve, boosts high neutralizing an????body ????ters in mice and non-human primates against both RSV and hMPV. The stable preF demonstrates enhanced stability under both refrigerated and elevated temperature condi????ons. The stable preF design is a promising op????on as a foldon-independent candidate for a next-genera????on RSV and hMPV vaccine.
