The attenuated virus in oral polio vaccines has developed the ability to evolve and spread to humans. Now, investigators have developed a new vaccine without the ability to make such changes.
Raul Andino, PhD
In much of the world, polio is thought of as a bygone disease—a threat that seems to belong in the history books. However, the virus itself has continued to evolve in dangerous ways, and the polio vaccine itself is actually part of the problem.
In a recently published study, investigators explained how the attenuated virus in the Sabin oral polio vaccine changed—and how they developed a new vaccine that limits the risk of such evolution. The results could have implications for the final push to eradicate polio, and might also affect how vaccine developers create vaccines for conditions like coronavirus disease 2019 (COVID-19).
Writing in the journal Cell Host & Microbe, Raul Andino, PhD, of the University of San Francisco, and Andrew Macadam, PhD, of the National Institute for Biological Standards and Control in the UK, report on the phase 1 results of a study of their new oral vaccine: the first new oral polio vaccine in 50 years.
The vaccine was designed to solve an emerging problem: in some parts of the world with low vaccination rates, weakened virus from the vaccine has been able to evolve and spread from vaccinated people to other individuals.
The effort came as a result of research by Andino and colleagues back in 2017, which found the vaccine virus had made 3 evolutionary changes that had enabled it to spread outside of its host. In response, Andino, Macadam, and colleagues decided to redesign the vaccine to stabilize the part of its viral genome that facilitates evolution.
They hope these changes will disable any ability of the virus to adapt in a way that could be harmful to humans.
“To my knowledge, this is the first effort to rationally design a live attenuated virus based on detailed understanding of its biology, as opposed to the standard approach of blindly passaging the virus in animal cells to eliminate human virulence through poorly understood mechanisms,” Andino said in a statement.
In the study, the investigators recruited 15 patients who had previously been vaccinated against polio and performed a test. The team exposed mice to viral samples from the stools of vaccinated humans to see whether or not the samples shed by humans could harm the mice. In earlier research, patients who were given the standard Sabin oral polio vaccine shed viral samples that caused paralysis in as many as 90% of mice.
In the new study, when the previously vaccinated volunteers were given the new oral vaccine, their viral samples proved unable to infect or cause paralysis in the mice.
Investigators are currently conducting a phase 2 trial, and the World Health Organization (WHO) is planning a phase 3 trial.
Andino hopes this research will also have an impact on newer vaccines. Most pressingly, while he notes that the race to develop a COVID-19 vaccine will likely rest on older vaccine-development technologies, he believes a longer-term solution might require the kinds of tailored vaccine-design technology demonstrated in this new research.
“Given how little we know about this new coronavirus,” he said, “I’m betting we’ll need all the weapons we can muster.”