Using attenuated, live viruses as vaccines is a promising strategy to reduce the impact of viral infectious diseases, such as influenza. Traditional live-attenuated virus vaccines have, however, often been limited due to suboptimal immunogenicity (the ability to invoke an immune response), safety
Schematic illustration of the generation of PROTAC viruses . Credit: Longlong Si
Traditional live-attenuated virus vaccines have, however, often been limited due to suboptimal immunogenicity , safety concerns, or cumbersome manufacturing processes and techniques. Additionally, immune escape due to rapid viral evolution poses a further challenge for traditional influenza vaccines.
The PTD was designed to contain a proteasome-targeting peptide and a tobacco etch virus cleavage site linker. It was used to selectively induce proteasomal degradation of viral proteins of interest; however, the TEVcs linker could be selectively cleaved by the tobacco etch virus protease to separate the viral proteins from the PTD, thus sparing them from degradation.
In mouse and ferret models, PROTAC viruses were sufficiently attenuated but able to elicit robust and broad humoral, mucosal, and cellular immunity. As a result, they provided broad protection against homologous and heterologous virus challenges.
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