Protein-Degradation Machinery is Harmful to a Viral Vaccine

Protein-Degradation Machinery is Harmful to a Viral Vaccine ...

Researchers have devised a promising new approach for generating live-attenuated viral vaccines. Their approach, which uses PROTAC technology to stimulate host cells to degradation viral proteins, was shown to induce strong immune responses in animal models.

The findings have been published in the journalNature Biotechnology. A paper titled Generation of a live attenuated influenza A vaccine by proteolysis targeting

Longlong Si, PhD, of the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences, has investigated alternative approaches to developing live-attenuated vaccinations.

The Sis team concluded that viral replication and the spread of infection are dependent on the stability of virally encoded proteins. They speculated that using the host cell's protein-degradation machinery to alter viral proteins' stability after infection might represent a viable novel approach for developing live-attenuated viral vaccines.

influenza A viruses were engineered in a manner that after infecting host cells, the viral proteins were destroyed or live attenuated by the host. In mouse and ferret models, the engineered viruses were shown to induce robust and broad immune responses.

The researchers' success is based on the proteolysis targeting chimeric (PROTAC) technique, an effective protein-degradation technique developed in recent years. These viruses were then fused to a conditionally removable proteasome-targeting domain (PTD) during vaccine development. These cell lines express an enzyme that removes the PTD from the viral proteins, thus making them safer and more effective vaccines, according to the researchers.

The success of their approach is based on proteolysis targeting chimeric (PROTAC) technology, an innovative protein-degradation technique developed in recent years. It leverages the cell's normal ubiquitin-proteasome machinery to remove undesirable proteins.

PROTAC viruses were designed by the Sis team, in which influenza viral proteins were fused to a conditionally removable proteasome-targeting domain (PTD) in conventional cells. When these viruses invaded conventional cells, they were killed by the host protein degradation machinery.

The researchers also created stable cell lines that preserve the PROTAC viruses' reproductive potential during vaccine development. These cell lines express an enzyme that removes the PTD from viral proteins, thus preventing degradation.

According to the researchers, this PROTAC vaccine technology might be a promising and universal method for generating safer and more effective vaccinations. It is a simple and general approach, potentially applicable to many other viruses, and readily accessible to most laboratories.

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