New Method To Prevent Diseases Caused By DNA Viruses
Rutgers researchers have designed a novel way to prevent viral infections: a live-attenuated, replication-defective DNA virus vaccine that employs the substance centanamycin to create an altered virus for vaccine production.
The procedure was tested in order to create a weaker or “attenuated” version of a common virus, mouse cytomegalovirus, that has been changed such that it cannot multiply or replicate inside the cell. A replication-defective DNA virus is unable to replicate its genome or genetic material. As a result, it is unable to create an infectious progeny virus in infected cells and is thus confined 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 team published the research, A chemical method for generating live-attenuated, replication-defective DNA viruses for vaccine development in the journal Cell Reports Methods.
“We discovered that this method is safe; the attenuated virus infects specific cells without proliferating beyond that and alerts the host to produce specific neutralising antibodies against it,” said Dabbu Jaijyan, an author of the study and a researcher in the Department of Microbiology at Rutgers New Jersey Medical School. “We see this as a revolutionary strategy that we believe may speed up the development of vaccines for many untreated viral diseases in people and animals.”
The approach for DNA viral vaccination
The approach is known as a live-attenuated DNA viral vaccination because it particularly targets DNA viruses (viruses that reproduce by generating copies of their DNA molecules, such as cytomegalovirus, chicken pox, and herpes simplex) and employs an altered DNA virus to attack them. The researchers believe that developing a mechanism for swiftly and readily producing replication-defective live-attenuated viruses may speed up vaccine development for illnesses caused by DNA viruses.
The approach has been demonstrated in mice to be effective against various DNA viruses, including human cytomegalovirus, mouse cytomegalovirus, and herpes simplex virus 1 and 2.
“One of the key benefits of our technique is the safety provided by the powerful prevention of viral reproduction and the absence of offspring viruses,” Jaijyan added. “We can readily use our approach to any DNA virus to manufacture live-attenuated replication-deficient viruses for vaccine development.”
This is not the case for all viruses. The COVID-19 virus, SARS-CoV-2, for example, is classified as an RNA virus since it replicates itself using RNA. COVID vaccines make use of this. SARS-CoV-2 uses RNA, which stands for ribonucleic acid, to construct proteins.
The DNA viral vaccination approach only works with DNA viruses because the researchers utilise centanamycin to treat the cytomegalovirus particles that would be used in the vaccine. The molecule is known as a DNA binder because it binds to the DNA of organisms, including DNA viruses, preventing reproduction.
The researchers want to someday test the approach on humans in order to cure cytomegalovirus and other DNA-virus diseases.
Cytomegalovirus virus
According to the Centers for Disease Control and Prevention, cytomegalovirus is a virus that affects people of all ages (CDC). The immune system of a healthy individual normally prevents the virus from developing sickness. Infection with CMV, on the other hand, can have serious effects on immunocompromised and organ transplant recipients. Congenital infection is also the major cause of neonatal birth abnormalities.
The virus is transmitted by bodily fluids such as blood, saliva, urine, sperm, and breast milk. According to the Centers for Disease Control and Prevention and the World Health Organization, CMV has infected nearly half of all individuals worldwide. By the age of five, one in every three children in the United States had been infected with the virus.
Experimentation procedure
The researchers generated cytomegalovirus samples in their lab, purified them, and then bathed them in centanamycin for the experiment. The weakened virus infects cells but does not spread after being put into lab mice. The mouse immune system eventually developed enough antibodies to shut down the virus and remove the infection.
The study verified that the treated viral cells were not hazardous to the mouse’s other cells.
The researchers are continuing to test the technology in additional medically significant viruses, such as guinea pig CMV as a model to evaluate vaccination efficacy in guinea pigs, with the goal of transferring the method into clinical trials to examine its efficiency in people.
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