Rutgers scientists have developed a new approach to stopping viral infections: a so-called live-attenuated, replication-defective DNA virus vaccine that uses a compound known as centanamycin to generate an altered virus for vaccine development.

 

The method was tested to produce a weakened or "attenuated" version of a mouse cytomegalovirus, a common virus, that has been altered so it can't reproduce or replicate inside the cell. A replication-defective DNA virus is incapable of replicating its genome, its essential genetic matter. As a result, it is unable to produce an infectious progeny virus in infected cells, and thus restricted primarily to the site of inoculation.

 

When the weakened viral particles are injected into animals, the researchers said, they stimulate a specific host's immune system to recognize the invading live virus particles as foreign, causing the virus to be eliminated whenever it is detected.

 

The new approach, published in Cell Reports Methods, has been shown to effectively shut down viral infections in lab animals.

 

"We have found that this method is safe; the attenuated virus infects certain cells without proliferating beyond that, and alerts the host to produce specific neutralizing antibodies against it," said Dabbu Jaijyan, a researcher in the Department of Microbiology at Rutgers New Jersey Medical School and an author of the study. "We see this as a novel method that we hope will accelerate vaccine development for many untreated viral infections in humans and animals."

 

The method is called a live-attenuated DNA virus vaccine because it specifically targets DNA viruses -- viruses such as cytomegalovirus, chicken pox and herpes simplex that reproduce by making copies of their DNA molecules -- and uses an altered DNA virus to fight against them. Developing a method that can quickly and easily generate replication-defective live-attenuated viruses, the researchers said, will accelerate vaccine development for diseases caused by DNA viruses.