Cell sub-issue: Development of a live-in attenuated DNA virus vaccine against DNA virus infection

In a new study, researchers from Rutgers University and Georgia State University in the United States have developed a new way to stop viral infections: a so-called live-attenuated, replicate-defective DNA virus vaccine that uses a compound called centanamycin to generate a modified virus for vaccine development
。 The findings were recently published in the journal Cell Reports Methods as "A chemical method for generating live-attenuated, replication-defective DNA viruses for vaccine development
.
"

When tested, the method produced a weakened or "attenuated" version of mouse CMV, a common virus that has been modified not to proliferate or replicate
intracellularly.
A DNA virus with replication defects cannot replicate its genome
.
Therefore, it is unable to 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 virus particles as foreign, causing the virus to be destroyed whenever detected
, the authors said.
This new method has been shown to be effective in shutting down viral infections
in laboratory animals.

Dabbu Jaijyan, co-corresponding author and a researcher in the Department of Microbiology at Rutgers University's New Jersey School of Medicine, said, "We found this method to be safe; Abridged viruses infect certain cells without proliferating and alert the host to produce specific neutralizing antibodies
against it.
We think this is a new approach, and we hope it will accelerate the development of
vaccines against many untreated viral infections in humans and animals.
”

The method is called a live-in attenuated DNA virus vaccine because it specifically targets DNA viruses--- viruses such as cytomegalovirus, chickenpox virus, and herpes simplex virus that proliferate by copying their DNA molecules, and uses modified DNA viruses to fight their infection
.
The authors say that developing a method that can quickly and easily produce a live attenuated virus with replication defects will accelerate vaccine development
against diseases caused by DNA viruses.

The authors demonstrated that the method was effective in mice against several DNA viruses, including human cytomegalovirus, mouse cytomegalovirus, herpes simplex virus type 1, and herpes simplex virus type 2
.

"One of the main advantages of our technology is the safety provided by the strong inhibition of viral replication and the absence of offspring virus
," Jaijyan said.
Our technology can be easily applied to any DNA virus to produce a live virus with replication defects for vaccine development
.
”

Not all viruses replicate
in this way.
For example, SARS-CoV-2, the coronavirus that causes COVID-19, belongs to the RNA virus because it produces a new copy
of itself through its RNA.
Vaccines against COVID-19 take advantage of this
.
RNA is used to build proteins
in SARS-CoV-2.

Image from Cell Reports Methods, 2022, doi:10.
1016/j.
crmeth.
2022.
100287
.

This live-in attenuated DNA virus vaccine approach is particularly suitable for DNA viruses because the authors treated CMV particles
intended for vaccine development with centanamycin.
This compound is a DNA binder because it grabs the DNA of an organism (including DNA from viruses) and prevents viruses or cells from proliferating
.
They hope to eventually test the approach in humans, with the aim of treating cytomegalovirus and other DNA virus infections
.

According to the Centers for Disease Control (CDC), cytomegalovirus is a common virus
that infects people of all ages.
A healthy person's immune system usually keeps the virus from causing disease
.
However, CMV infection can have serious consequences
for immunocompromised humans and organ transplant patients.
Congenital cytomegalovirus infection is also a major cause
of birth defects in newborns.

CMV is transmitted through bodily fluids, including blood, saliva, urine, semen, and breast milk
.
According to the CDC 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, these authors cultured CMV samples in the lab, purified them, and then soaked them in
centanamytin.
Once injected into laboratory mice, the attenuated CMV infects cells but does not spread
.
Over time, the mouse immune system produced enough antibodies to shut down the virus and eliminate the infection
.
An analysis confirmed that these attenuated CMV-infected cells were not toxic
to other cells in mice.

The authors are continuing to test this approach in other medically significant DNA viruses--- including guinea pig cytomegalovirus --- as a model for testing the efficacy of guinea pig vaccines, and intend to enter clinical trials to test its effectiveness
in humans.
(Biovalley Bioon.
com)

Resources:

Dabbu Kumar Jaijyan et al.
A chemical method for generating live-attenuated, replication-defective DNA viruses for vaccine development, Cell Reports Methods, 2022, doi:10.
1016/ j.
crmeth.
2022.
100287.