New era in respiratory virus protection: Molecular clamping

Molecular clamping in vaccine development refers to a technology that uses a specially designed polypeptide (the “molecular clamp”) to stabilize viral proteins, particularly their pre-fusion conformations, which are the forms most recognized by the immune system for neutralizing viruses. Many viral surface proteins (such as spike proteins on coronaviruses or hemagglutinin on influenza) change shape (from “pre-fusion” to “post-fusion”) once they fuse with the host cell. The pre-fusion state is typically the most potent form for inducing protective immune responses, but it is unstable and difficult to maintain outside of the virus. Molecular clamp technology links a stable trimerization domain to the viral protein, holding it in the pre-fusion (native) shape. This ensures the immune system “sees” the relevant structure, improving vaccine effectiveness. The clamp is made up of sequences that self-assemble into a stable helical structure and is genetically fused to the viral protein fragment of interest. This approach has been successfully applied to multiple viruses, including influenza, RSV, Ebola,...