Growing live virus to make polio vaccines was a necessary risk, but that may be about to change

A new vaccine production method uses harmless polio protein shells, bypassing the need to work with live poliovirus.

Polio is nearly eradicated, but we grow huge quantities of poliovirus to make vaccines against it. That’s fine as long as the virus stays in the production plant, but the risk it could accidently escape and become reintroduced into the human population makes this approach less than ideal. Now, newly published research offers a solution: a way to make an effective vaccine without a live virus. Virologist Andrew Macadam of the National Institute for Biological Standards and Control (NIBSC) tells us more.  

ResarchGate: What's dangerous about current methods of producing polio vaccines?

Andrew Macadam: The risk has to do with the context of vaccine production. The world today has all but eradicated the disease, but the polio vaccines in current use require growth of the virus. Producing the injectable vaccine (IPV) involves growing very large quantities of live poliovirus, which is then inactivated. This presents a serious containment issue since, if poliovirus accidentally escaped from a production plant, it could result in re-introduction of the virus into the human population. Clearly this poses a risk to the long-term success of the polio eradication program.

Polio vaccine production
IPV polio vaccine being proudced with current methods. Credit: Sanofi Pasteur / Norbert Domy

RG: How is the new method different?

Macadam: Because of this risk, it is highly desirable to develop a vaccine which does not involve infectious poliovirus at any stage in the production process. This could be achieved by synthesizing “empty” particles, which are devoid of any genetic material—so are not infectious—but at the same time retain the ability to induce a protective immune response in humans.

RG: How did you achieve this, and why hasn’t it been done before?  

Macadam: Naturally occurring and synthetic empty particles are extremely thermally unstable outside the cell. They lack some of the inter-subunit interactions that hold mature virus particles together. As a consequence, they are highly susceptible to protein rearrangements that change the shell into a form that is no longer able to trigger the desired immune response. Hence, naturally occurring empty particles are unsuitable for vaccine production.

To solve this problem, we developed a method to identify modifications that modulate particle stability. Introducing combinations of these modifications increased particle stability to a level compatible with vaccine production. The particles induced high levels of protective antibodies in animals and could be stored without refrigeration for many months without significant loss of activity.

RG: When do you expect this new procedure to be applied to vaccines used in the field?

Macadam: This work demonstrated that stable empty particles that trigger an immune response can be produced using whole virus genomes. The designs need to be transferred to production systems that use just the P1 precursor and 3CD viral protease before large scale production and vaccine trials can be considered. This work is ongoing in laboratories of our specialist collaborators working in a WHO-funded consortium. The results of this work are very promising.

Polio vaccines are packaged in a production facility. Credit: Sanofi Pasteur / Aiko Kawamura

RG: Are there other vaccines this approach could be applied to?

Macadam: The design approach we developed was remarkably effective and worked for all three types of polio. This suggests it may have applications in the design of vaccines against other virus diseases, particularly those caused by other enteroviruses which are structurally related to poliovirus.

RG: Are there circumstances in which polio virus should be grown?

Macadam: There have been many surprises during the polio eradication campaign, and there are still uncertainties about the future. So polio research—not only into new vaccines—is an important tool to keep using. For this reason, the clear need to contain polioviruses rigorously needs to be balanced against the practicalities of carrying out effective research.

Featured image courtesy of Sanofi Pasteur.