The poliovirus, which once paralyzed children across the globe, is nearly eradicated in nature. There were just 74 cases of polio reported in 2015, according to the World Health Organization, down from an estimated 350,000 in 1988.

Two vaccines contributed to this drastic decline in polio incidence – one contains a dead virus and the other a weakened form of the virus. Both involve the handling of the potentially dangerous live virus in the production process. “Although these [vaccine production facilities] are very good and their containment measures are extremely well implemented, there is always the hazard that there could be an escape,” says virologist Andrew Macadam of the National Institute for Biological Standards and Control in the United Kingdom

To stave off this threat, Macadam and colleagues are working to develop a new polio vaccine that could be produced without the live virus. As they report in PLOS Pathogens, the researchers recently made a crucial advance: They were able to circumvent the virus’s biological quirks to devise an essentially virus-free vaccine that successfully protected mice from the disease.

Like all viruses, the poliovirus has an outer shell known as a capsid that contains the virus’s genetic material. The scientists wanted to create an empty capsid that would prompt an immune response without exposing patients to the genetic material that allows the virus to spread. This same technique was used to develop vaccines for hepatitis B and the human papillomavirus.

The trouble is, unlike these other virus capsids, once the polio capsid is stripped of its genetic innards, it changes shape. When the body’s B cells encounter this new shape, they produce the wrong antibody response, and so cannot protect against the polio virus.

Seeking a way to stabilize the capsid, Macadam and his team first generated mutant viruses that were capable of producing a more stable empty capsid. By sequencing these mutants, they identified a range of capsid stabilizing mutations. The researchers then inserted different numbers and combinations of these mutations into the viral genome until they found a virus that produced a stable empty capsid.

There are in fact three different types of poliovirus, and the team was able to create stable empty capsids of each by inserting 5, 7, or 8 mutations into the viral genomes. An injection of these empty capsids protected mice from the poliovirus.

But to make these empty capsids, Macadam still had to start with the live virus. He is now working with a consortium of scientists to find a way to make yeast, mammalian cells, or even plant cells produce the empty polio virus capsids. Such a system would eliminate the need for live virus in the lab, and also enable them to scale up production.

Producing a polio vaccine without the live virus has long been the “holy grail,” says Peter Wright, chair of the Polio Research Committee at the Global Polio Eradication Initiative at the World Health Organization, which helped support the study. “To have work like this published now is a very important step,” he says.

Still, a human version of the vaccine remains a long way off, says Neal Halsey, director of the Institute for Vaccine Safety in the Department of International Health at the Johns Hopkins Bloomberg School of Public Health, who was not involved the study. One challenge is that researchers can’t conduct the traditional Phase III clinical trials in humans to demonstrate vaccine efficacy because too few people currently have polio. “There is a great deal of work to be done,” he says. “But this is a very promising approach to making a vaccine that we should have.”