With only 74 cases reported worldwide in 2015 (all in Afghanistan and Pakistan) poliomyelitis eradication is in sight. However, polio vaccines will be required for the foreseeable future to prevent re-emergence of the disease, and such vaccines need to be safe, effective, cheap, and easy to deliver. A study published in PLOS Pathogens reports the generation of promising new cold-adapted vaccine strains that are unable to multiply at the temperature of the human body and therefore highly unlikely to cause poliomyelitis in humans.
To minimize the risks associated with post-eradication vaccine manufacturing, stockpiling, and delivery, WHO and its collaborators would like to see conventional inactivated polio vaccine (cIPV, which is made from polio virus strains that, before they are inactivated, can cause poliomyelitis) replaced with an IPV made from attenuated (non-disease-causing) polio strains. Barbara Sanders, from Janssen Infectious Diseases and Vaccines in Leiden, The Netherlands, and colleagues set out to develop novel attenuated polio virus strains. Their goal was to develop strains for affordable IPV manufacture that can address the biosafety issues of cIPV without compromising its high immunogenicity (i.e., the ability to induce a strong and lasting immune response).
The researchers’ approach was to attenuate polio virus by adapting it to grow below the 37°C (98.6 degrees Fahrenheit), the normal body temperature for humans. They then looked for strains that would grow well at lower temperatures, were unable to grow at 37°C or higher, and could induce potent antiviral immunity after being inactivated.
The researchers started by selecting virus strains that grew well at low temperature (26-30°C) in a cell line suitable for vaccine manufacture. After several rounds of selection, they isolated three different virus clones and sequenced their genomes. Each clone had acquired multiple mutations, and the researchers then used genetic engineering to combine a total of 31 mutations from the three clones into one synthetic viral genome. The resulting virus grew well at 30°C but was completely unable to grow at 37°C.
Next, they then combined this virus with genes from cIPV viruses that code for the virus outer shell and are responsible for generating a strong and polio-specific immune response. Like the parental strains, these CAVA (for Cold-Adapted Viral Attenuation) viruses were unable to grow at 37°C, and they maintained this absolute temperature block even after prolonged time in the 37°C environment. In contrast, the CAVA strains grew well at 30°C in the vaccine manufacture cell line, suggesting that they could be produced at low cost for an affordable vaccine.
Electron micrograph image of a cell after infection with a CAVA polio virus strain at 30°C
Image Credit: Sanders et al.