Chemically attenuated live DNA virus vaccine prevents viral infection

Rutgers researchers have devised a new way to prevent viral infections: a live-attenuated, replication-defective DNA virus vaccine that utilizes the substance centanamycin to create an altered virus for vaccine development.

The procedure was tested in order to create a weakened or “attenuated” version of a common virus, mouse cytomegalovirus, that has been modified 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 attenuated viral particles are injected into animals, they trigger a certain host's immune system to identify the intruding live virus particles as foreign, enabling the virus to be eradicated whenever it is discovered, according to the researchers.

The novel method, which was reported in Cell Reports Methods, was found to efficiently prevent 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. We see this as a novel method that we hope will accelerate vaccine development for many untreated viral infections in humans and animals.

Dabbu Jaijyan, Study Author and Researcher, Department of Microbiology, New Jersey Medical School, Rutgers University

The method is referred to as a live-attenuated DNA virus vaccine because it specifically targets DNA viruses—viruses that multiply by generating copies of their DNA molecules, such as cytomegalovirus, chicken pox, and herpes simplex—and utilizes an altered DNA virus to attack them.

The researchers believe that developing a mechanism for swiftly and easily producing replication-defective live-attenuated viruses will speed up vaccine development for diseases 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 major advantages of our technology is the safety offered by the robust inhibition of virus replication and that no progeny viruses are produced. Our technology can be easily applied to any DNA virus to generate live-attenuated replication defective viruses for vaccine development.”

Dabbu Jaijyan, Study Author and Researcher, Department of Microbiology, New Jersey Medical School, Rutgers University

This is not the case for all viruses. The COVID-19 virus, SARS-CoV-2, for instance, is characterized as an RNA virus since it replicates itself using RNA. COVID vaccines take advantage of this fact. SARS-CoV-2 uses RNA, which stands for ribonucleic acid, to produce proteins.

The DNA viral vaccination approach only works with DNA viruses because the researchers utilize 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 hope to someday test the approach on humans to treat cytomegalovirus and other DNA-virus infections.

According to the Centers for Disease Control and Prevention (CDC), cytomegalovirus is a virus that affects people of all ages. The immune system of a healthy person normally prevents the virus from developing an illness. Infection with cytomegalovirus, on the other hand, can have serious effects on immunocompromised and organ transplant recipients. Congenital infection is also the major cause of newborn birth abnormalities.

The virus is transmitted through bodily fluids such as blood, urine, saliva, semen, and breast milk. According to the CDC and the World Health Organization, cytomegalovirus 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.

The researchers grew cytomegalovirus samples in their laboratory, 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.

An analysis verified that the treated viral cells were not hazardous to the mouse’s other cells.

The scientists are proceeding to test the technology in additional medically significant viruses, such as guinea pig cytomegalovirus as a model to test vaccination efficacy in guinea pigs, with the goal of transferring the method into clinical trials to examine its efficiency in humans.

Source:
Journal reference:

Jaijyan, D. B., et al. (2022) A chemical method for generating live-attenuated, replication-defective DNA viruses for vaccine development. Cell Reports Methods. doi.org/10.1016/j.crmeth.2022.100287.

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