Production of "DNA virus vaccines" to fight DNA viruses

Rutgers scientists have developed a new way to stop viral infections: a so-called live, replicated, defective DNA virus vaccine that uses a compound called centanamycin to create a mutated virus for vaccine development
.

After testing, this approach produced a weakened or "attenuated" version of mouse CMV, a common virus that, with modification, cannot multiply or replicate
inside cells.
DNA viruses with defective replication cannot replicate their basic genetic material, the genome
.
Therefore, it cannot produce infectious offspring viruses in infected cells and is therefore mainly limited to the inoculation site
.

When weakened viral particles are injected into animals, they stimulate the immune system of a particular host to recognize the invading live viral particles as foreign, allowing the virus to be destroyed
when detected, the researchers said.

The new method, published in the journal Cell Reports Methods, has been shown to be effective in stopping viral infections
in laboratory animals.

"We found this method to be safe; Attenuated viruses infect certain cells but do not proliferate and alert the host to produce specific neutralizing antibodies," said
Dabbu Kumar, a researcher in the Department of Microbiology at Rutgers University School of Medicine in New Jersey and author of the study.
"We think this is a new approach, and we hope it will accelerate the development of vaccines to treat many untreated viral infections
in humans and animals.
"

This method is called a live attenuated DNA virus vaccine because it specifically targets DNA viruses (such as cytomegalovirus, chickenpox, and herpes simplex virus that multiply by copying DNA molecules) and uses modified DNA viruses to fight them
.
The researchers say that developing a method that can quickly and easily produce live attenuated viruses with replication defects will accelerate vaccine development
against diseases caused by DNA viruses.

Researchers have demonstrated that this approach is effective against several DNA viruses in mice, including human cytomegalovirus, mouse cytomegalovirus, and herpes simplex viruses No.
1 and 2
.

"One of the main advantages of our technology is the security provided by powerful inhibition of viral replication, which does not produce offspring viruses
," Jaijyan said.
Our technology can be easily applied to any DNA virus to produce attenuated replication defective viruses for vaccine development
.
”

Not all viruses replicate
in this way.
For example, the COVID-19 virus SARS-CoV-2 is called an RNA virus because it produces new copies
through its own RNA.
COVID vaccines take advantage of this
.
RNA, short for ribonucleic acid, is used to build proteins
in SARS-CoV-2.

The DNA virus vaccine method is particularly applicable to DNA viruses because the researchers treated CMV particles
used in the vaccine with centanamycin.
This compound is called a DNA binder because it attaches to an organism's DNA, including DNA from viruses, preventing reproduction
.

The team hopes to eventually test this approach in humans to treat cytomegalovirus and other DNA infections
.

According to the Centers for Disease Control and Prevention (CDC), cytomegalovirus is a common virus
in people of all ages.
A healthy person's immune system normally stops the virus from causing illness
.
However, CMV infection can have serious consequences
in immunocompromised and organ transplant patients.
Congenital infections are also a leading cause of
birth defects in newborns.

The virus is transmitted through bodily fluids, including blood, saliva, urine, semen and breast milk
.
According to the Centers for Disease Control and Prevention and the World Health Organization, about 50% of adults worldwide are infected with CMV
.
In the United States, one in three children is infected with the virus
before the age of five.

In experiments, the researchers cultured CMV samples in the lab, purified them, and then soaked them in
centanamycin.
Once injected into mice, the weakened virus infects cells but does not spread
.
Over time, the mouse's immune system produced enough antibodies to shut down the virus and eliminate the infection
.

One analysis confirmed that the treated viral cells were not toxic
to other cells in mice.

The researchers are continuing to test the method on other medically important viruses, including guinea pig cytomegalovirus as a model, to test the vaccine's effectiveness in guinea pigs, and intend to conduct clinical trials to test the method's effectiveness
in humans.

Dabbu Kumar Jaijyan, Kavitha Govindasamy, Moses Lee, Hua Zhu.
A chemical method for generating live-attenuated, replication-defective DNA viruses for vaccine development.
Cell Reports Methods, 2022; 2 (9): 100287