A promising strategy to reduce the impact of viral infectious diseases, such as influenza, is the use of attenuated, live viruses as vaccines.
However, the usefulness of traditional live-attenuated virus vaccines has often been limited by suboptimal immunogenicity, safety concerns, or cumbersome manufacturing processes and techniques. In addition, immune escape due to rapid viral evolution poses a further challenge for traditional influenza vaccines.
Recently, a research team has proposed a new live-attenuated influenza vaccine approach — generating proteolysis-targeting chimeric (PROTAC) influenza A virus as a live-attenuated vaccine by utilizing the endogenous ubiquitin-proteasome system of host cells to degrade viral proteins. The results were published in Nature Biotechnology.
Given that virus replication depends on virally encoded proteins, manipulation of viral protein stability by utilizing the protein degradation machinery of the host cell may represent a potential approach to switch the viral life cycle on and off for vaccine development. Thus, the researchers designed proteolysis-targeting chimeric (PROTAC) viruses by fusing a conditionally removable proteasome-targeting domain (PTD) to influenza viral proteins.
The PTD was designed to contain a proteasome-targeting peptide and a tobacco etch virus cleavage site (TEVcs) 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 (TEVp) to separate the viral proteins from the PTD, thus sparing them from degradation.
Accordingly, the researchers engineered the genome of influenza A viruses in TEVp-expressing stable cell lines engineered for virus production to introduce the conditionally removable PTD, generating fully infective PROTAC viruses that were live-attenuated by the host protein degradation machinery upon infection.
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.
"This PROTAC vaccine technology could also be useful for generating live-attenuated vaccines against other types of pathogens," said the senior author.
https://www.nature.com/articles/s41587-022-01381-4
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fgeneration-of-a-live&filter=22
A new live-attenuated influenza A vaccine
- 1,099 views
- Added
Latest News
Human Microglial State Dyna…
By newseditor
Posted 05 Dec
Giant immune cells compensa…
By newseditor
Posted 05 Dec
Menopausal hormone changes…
By newseditor
Posted 05 Dec
Humans can intermittently r…
By newseditor
Posted 04 Dec
Why young kids don't get se…
By newseditor
Posted 04 Dec
Other Top Stories
A shuttle protein required for the nuclear import of proteins essen…
Read more
Molecular debris clearing protein can clump into fibrils!
Read more
Single test for over 50 genetic neuromuscular diseases
Read more
A protein involved in aging and alters cellular senescence identifi…
Read more
Why women are more susceptible to Alzheimer's Disease
Read more
Protocols
Brain-wide circuit-specific…
By newseditor
Posted 05 Dec
Cheap, cost-effective, and…
By newseditor
Posted 03 Dec
Temporally multiplexed imag…
By newseditor
Posted 02 Dec
Efficient elimination of ME…
By newseditor
Posted 01 Dec
Personalized drug screening…
By newseditor
Posted 30 Nov
Publications
Human microglial state dyna…
By newseditor
Posted 05 Dec
Eating disorders: are gut m…
By newseditor
Posted 05 Dec
Cancer cells reprogram to m…
By newseditor
Posted 05 Dec
Estrogen receptor beta in a…
By newseditor
Posted 05 Dec
Microbiota from Alzheimer's…
By newseditor
Posted 05 Dec
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar