First steps to eradicate polio with a new generation of vaccines

Although polio vaccines have been essential in containing the ravages of this infectious disease, the goal of eradicating it is proving to be more elusive than was estimated decades ago.. US researchers from the University of California at San Francisco and the Centers for Disease Control and Prevention in Atlanta publish in Nature the results of their work on developing vaccines that pave the way for the disappearance of the disease.

Poliovirus consists of three serotypes capable of causing poliomyelitis.. Thanks to vaccines, it has been possible to eradicate wild poliovirus types 2 and 3 (WPV2 and WPV3, for its acronym in English). However, the WPV1 serotype still causes outbreaks with some frequency in Afghanistan and Pakistan.. There is also concern about the circulation of vaccine-derived poliovirus (VDPV) strains and cases of vaccine-associated paralytic poliomyelitis, which is a rare complication of oral vaccination..

How many vaccines are there against polio?

Two types of vaccines are currently used against poliomyelitis: the injectable inactivated virus (Salk vaccine) and the oral attenuated virus (OPV or Sabin vaccine).. Among oral vaccines, the new and recent vaccine against type 2 poliomyelitis (nOPV2) stands out, which is a modified version of the monovalent oral vaccine of the same type (mOPV2)..

nOPV2 is also an attenuated virus vaccine, which has shown efficacy in inducing an immune response, but it is genetically more stable thanks to the modification of specific points in the genome of the vaccine strain that prevent the virus from recovering its virulence. Its development has been possible thanks to the application of reverse genetics, an approach for vaccine development first described in 1981.. This technology enables its use against vaccine-derived poliovirus variants, decreases the chances of new ones emerging or causing vaccine-associated paralytic polio.

Based on this approach, the team led by Raul Andino (University of California) and Andrew Macadam (CDC) have designed new vaccines for the WPV1 and WPV3 serotypes (nOPV1 and nOPV3).. The authors used the genetic sequence of nOPV2 and incorporated genes encoding components of the protein coat structure of the OPV1 and OVP2 vaccine virus..

Their research in mice revealed that both vaccines were highly immunogenic and very safe.. The authors explain that they remain attenuated even if mutations occur after vaccination.. “Even in the worst case, where many mutations accumulate in the nOPV genomes, the resulting viruses are likely to be much more attenuated than wild-type polioviruses.”

What is the new protective shield to eradicate polio?

Furthermore, in their article they describe how the joint administration of nOPV1, nOPV2 and nOPV3 in mice resulted in the production of antibodies against the three poliovirus serotypes and the mice were protected against the disease..

“This finding indicates that there was no interference between the three viruses in terms of their ability to multiply simultaneously,” interprets Alan Barrett, from the Sealy Institute for Vaccine Sciences at the University of Texas, in an article commenting on Andino's progress. and Macadam also published in Nature. “Mouse model offers proof of concept that a trivalent nOPV vaccine could work in humans”.

To date, only two infectious diseases have been eradicated through vaccination: smallpox and rinderpest.. And in both cases it was thanks to live attenuated vaccines, Barrett recalls.

What will the trial in people be like?

These first preclinical results have allowed the start-up of a phase I trial with these vaccines, the results of which are expected to be available this year.. This first study in humans will give more clues about its safety profile, immunogenicity and genetic stability.. “Although nOPV1 and nOPV3 are currently in development for an outbreak response indication, it could be repurposed and used in campaigns in high-risk areas, or potentially even routinely, depending on epidemiological circumstances.”

Based on these results, the authors state that “poliovirus eradication is achievable”. Barrett agrees, calling the science behind these advances “impressive”

When the Initiative for the Global Eradication of Polio was launched in 1988, it was thought that it could be achieved by 2000.. Since 2013, this initiative has set priorities to eliminate WPV1 and manage cases of vaccine-derived poliovirus and cases of vaccine-associated paralytic poliomyelitis, for which new vaccines could be key. “After this, the risk of vaccine-derived type 1 and 3 viruses will need to be controlled in settings where gut immunity, which prevents virus spread, wanes over time,” the researchers warn.