Study offers insight into potentially problematic interactions between viruses and live vaccines

A study of the herpes virus infecting chickens offers new insight into the potentially problematic interactions between vaccines made from live viruses and viruses that are meant to be thwarted.

Reported in the journal Virulence, the study offers direct evidence that vaccines and viruses can infect the same cells in live animals and share the molecular tools that allow the virus to infect other animals – in this case, chickens.

The study focused on Marek’s disease, a viral infection that is spread when a chicken inhales flakes of dead skin or feather tissue from an infected chicken.

“We’ve been trying to understand how the virus spreads from one host to another,” said University of Illinois Urbana-Champaign pathobiology professor Keith Jarosinski, who led the study. “Not only did we do it for the benefit of chickens in the poultry industry, but also because of a very similar mechanism used by the virus that causes chickenpox, where it enters through the respiratory tract and infects lymphocytes, and that’s to the skin.”

The poultry industry has a practice of vaccinating newly hatched chickens against Marek’s disease virus, Gallid alphaherpesvirus 2. Some even vaccinate chicks in eggs, Jarosinski said. The use of live vaccines that have been modified to be non-infectious is the most effective strategy for controlling disease symptoms, which include failure to thrive, tumors, and death.

Vaccines made from live viruses do a better job than other vaccines at training the immune system to recognize the Marek’s disease virus, but they don’t lead to eradication of the virus, Jarosinski said. This leaves room for natural viruses and modified viral vaccines to interact in ways that could promote viral evolution or transmission.

Previous studies have shown that viruses can pick up genes from vaccines designed to fight them, allowing viruses to evolve in ways that sometimes increase virulence. But there are no studies showing that viruses and vaccines actually infect the same cells in live animals, Jarosinski said.

Another potential interaction between viruses and vaccines involves a process known as “complementation,” in which a vaccine, for example, produces molecules that the virus can use to help it become infectious or more infectious, he said.

The aim of the new study was to determine whether the vaccine and the natural virus could infect the same cells in live chickens and to track whether the vaccine could supply molecules that help the virus spread to healthy chickens.

To do this, the researchers used a combination of viruses and vaccines, some of which contain all the genes for transmission and some that are modified in such a way that they cannot infect new hosts. This sometimes involves deleting genes for proteins needed to enter cells and infect new hosts.

The researchers inoculated several chickens with both the virus and the vaccine and placed them with chickens that had not been exposed to either. Some of the inoculated birds were exposed to non-infectious forms of the virus and non-infectious vaccines. Some are inoculated with non-communicable viruses and infectious vaccines.

Vaccines are marked with red fluorescent molecules and non-infectious viruses are marked in green, allowing researchers to track the course of the vaccine and viral infection in cells. The combination of red and green fluorescence produces a yellow light, so only cells that glow yellow are infected with the virus and vaccine.

The study revealed that some of the cells in the inoculated birds contained both the virus and the vaccine — the first demonstration of this phenomenon in live animals, Jarosinski said.

The study also found that a Marek’s disease virus that lacks a particular molecule required for infection – in this case a protein on the virus’ outer envelope – is able to pick up that molecule from a vaccine that has infected the same cells. This allows the virus to infect new chicks.

“Other studies haven’t really shown that complementation between vaccines and viruses occurs except in artificial laboratory settings where they use human-specific herpes viruses in mice or pigs, for example,” Jarosinski said. “One of the unique things about this study is that we have seen this process in a more natural infection model, where we are using a virus that is specific to chickens in chickens.”

The study shouldn’t be used to spread alarm or panic, Jarosinski said, because complementation events are less worrying than viruses swapping genes for vaccines. But the findings should inform vaccine design to eliminate potential attributes that could aid the spread of the virus.

The US Department of Agriculture and the National Institutes of Health supported this research.

Source:

University of Illinois at Urbana-Champaign

Journal reference:

Xu, H., et al. (2022) Coinfection in the host can result in functional complementation between live vaccines and virulent viruses. Poisoning. doi.org/10.1080/21505594.2022.202082645.

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