Rational design of uncleaved prefusion-closed trimer vaccines for human respiratory syncytial virus and metapneumovirus.

ABSTRACT: Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) cause human respiratory diseases and are major targets for vaccine development. In this study, we design uncleaved prefusion-closed (UFC) trimers for the fusion protein (F) of both viruses by examining mutations critical to F metastability. For RSV, we assess four previous prefusion F designs, including the first and second generations of DS-Cav1, SC-TM, and 847A. We then identify key mutations that can maintain prefusion F in a native-like, closed trimeric form (up to 76%) without introducing any interprotomer disulfide bond. For hMPV, we develop a stable UFC trimer with a truncated F₂-F₁ linkage and an interprotomer disulfide bond. Dozens of UFC constructs are characterized by negative-stain electron

SUBMITTER: Lee YZ 

PROVIDER: S-EPMC11569192 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature