Rational design 2.0: transitioning from static structural biology to computational prioritization and iterative vaccine optimization for RSV

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RSV is a leading cause of severe lower respiratory tract disease in infants and older adults, resulting in millions of infections and significant mortality.
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The F protein of RSV transitions between prefusion and postfusion conformations, affecting the exposure of neutralizing epitopes critical for vaccine efficacy.
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Current vaccine candidates based on the F protein have shown limited efficacy due to antigenic instability and the virus's ability to evolve.
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Recent advances in computational protein design and protein language models enable improved stabilization of preF conformations for vaccine development.
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The proposed framework 'Rational Design 2.0' integrates structural and evolutionary information to enhance RSV vaccine design beyond static optimization.

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