Efficacious human metapneumovirus vaccine based on AI-guided engineering of a closed prefusion trimer.

ABSTRACT: The prefusion conformation of human metapneumovirus fusion protein (hMPV Pre-F) is critical for eliciting the most potent neutralizing antibodies and is the preferred immunogen for an efficacious vaccine against hMPV respiratory infections. Here we show that an additional cleavage event in the F protein allows closure and correct folding of the trimer. We therefore engineered the F protein to undergo double cleavage, which enabled screening for Pre-F stabilizing substitutions at the natively folded protomer interfaces. To identify these substitutions, we developed an AI convolutional classifier that successfully predicts complex polar interactions often overlooked by physics-based methods and visual inspection. The combination of additional processing, stabilization of interface regions an

SUBMITTER: Bakkers MJG 

PROVIDER: S-EPMC11272930 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature