A new study of a herpes virus that infects chickens sheds light on potentially problematic interactions between vaccines made from live viruses and the viruses they are designed to combat.
The study, which was published in the journal Virulence, provides direct evidence that a vaccine and virus can infect the same cells in living animals and share molecular tools that allow the virus to infect other animals – in this case, chickens.
Marek's disease is a viral infection that spreads when one chicken inhales fragments of dead skin or feather tissue from another infected chicken.
"We've been trying to understand how the virus spreads from one host to another," said Keith Jarosinski, a pathobiology professor at the University of Illinois Urbana-Champaign who led the research. "We're doing it not only for the benefit of chickens in the poultry industry, but also because it's a very similar mechanism that the virus that causes chickenpox uses, where it enters through the respiratory route, infects lymphocytes, and then gets to the skin."
Vaccinating newly hatched chickens against the Marek's disease virus, Gallid alphaherpesvirus 2, is a practice in the poultry industry. Some even vaccinate chicks in the egg, according to Jarosinski. The use of live vaccines that have been modified to be non-infectious is the most effective strategy for controlling disease symptoms such as failure to thrive, tumors, and death.
Vaccines made from live viruses perform better than other vaccines in training the immune system to recognize the Marek's disease virus, but they do not result in virus eradication, according to Jarosinski. This opens the door for natural viruses and modified viral vaccines to interact in ways that promote viral evolution or infectiousness.
Previous research has shown that viruses can acquire genes from vaccines designed to combat them, allowing viruses to evolve in ways that sometimes increase virulence. However, no studies have shown that viruses and vaccines infect the same cells in live animals, according to Jarosinski.
Another possible interaction between viruses and vaccines involves a process known as "complementation," in which vaccines, for example, produce a molecule that the virus can use to help it become more infectious, he said.
The researchers wanted to see if vaccines and natural viruses could infect the same cells in living chickens and if a vaccine could supply a molecule that helps the virus spread to healthy chickens.
To accomplish this, researchers used a combination of viruses and vaccines, some of which contained all of the genes required for transmission and others that were modified in ways that rendered them incapable of infecting new hosts. Occasionally, this entailed deleting the gene for a protein required to enter cells and infect the new host.
The chickens were inoculated with both a virus and a vaccine before being housed with chickens that had not been exposed to either. Some of the inoculated birds were given a nontransmissible version of the virus as well as a nontransmissible vaccine. Some were given a nontransmissible virus as well as a transmissible vaccine.
The vaccines were labeled with a red fluorescent molecule, while the nontransmissible virus was labeled with a green fluorescent molecule, allowing the researchers to monitor the progression of vaccine and viral infection in cells. Only cells that glowed yellow were infected with both the virus and the vaccine, as a combination of red and green fluorescence produces yellow light.
According to Jarosinski, the study revealed that some cells in inoculated birds contained both virus and vaccine – the first demonstration of this phenomenon in live animals.
The researchers also discovered that a Marek's disease virus lacking a specific molecule required for infection – in this case, a protein on the virus's outer envelope – could pick up that molecule from a vaccine that had infected the same cell. As a result, the virus was able to infect new chickens.
"Other studies haven't really shown that complementation between vaccines and viruses occurs except in artificial laboratory circumstances, such as using human-specific herpes viruses in mice or pigs," Jarosinski explained. "One of the unique aspects of this study is that we examined this process in a more natural model of infection, in which we used a virus-specific to chickens in chickens."
According to Jarosinski, the study should not be used to spread fear or panic because complementation events are less concerning than viruses swapping genes with vaccines. However, the findings should guide the development of vaccines to eliminate potential characteristics that aid virus spread.