Phase
1 trial shows promise for completion of stalled eradication effort; offers
lessons for COVID-19 vaccine development.
Virologists
report promising Phase 1 clinical results for the first new oral polio vaccine
in 50 years, which they have designed to be incapable of evolving the ability
to cause disease in humans.
Before
being halted due to the COVID-19 pandemic, a relentless vaccination campaign
had nearly succeeded in eradicating polio from the world. Between 2000 and
2017, the World Health Organization (WHO) estimated that its campaign had reduced
the burden of the disease by 99 percent, preventing more than 13 million
children from becoming infected and risking potentially debilitating paralysis.
But
in recent years, the eradication effort has been plagued by outbreaks of
vaccine-derived polio -- in which the weakened virus used in oral polio
vaccines evolved the ability to escape from vaccinated individuals and spread
in communities with poor vaccination rates.
Now,
with support from the Bill and Melinda Gates Foundation, UC San Francisco virologist
Raul Andino, PhD and Andrew Macadam, PhD, of the UK's National Institute for
Biological Standards and Control (NIBSC) report promising Phase 1 clinical
results for the first new oral polio vaccine in 50 years, which they have
designed to be incapable of evolving the ability to cause disease in humans.
In a
2017 study, Andino and colleagues discovered that in every vaccine-derived
polio outbreak they studied, the virus had used the same three evolutionary
steps to mutate from harmless vaccine into a regional menace.
In their new study, Andino, Macadam,
and colleagues at the Gates Foundation, the Center for Vaccine Innovation and
Access in Seattle, and the Centre for the Evaluation of Vaccination at the
University of Antwerp have employed clever genetic wizardry based on decades of
study of the poliovirus's biology to redesign the vaccine to ensure that is
incapable of following this three-step pathway to re-evolve virulence.
Specifically, they stabilized a region of the viral genome that is required for
it to re-evolve the ability to infect humans, and ensured that the virus could
not get rid of this modification even by exchanging genetic material with
related viruses.
The
trial found that the new designer polio vaccine was both more stable and more
effective than the 50-year old Sabin vaccine from which it was derived.
Specifically, the new vaccine caused participants to generate plentiful antibodies
against the poliovirus, and despite shedding viral particles in their stool,
those particles were unable to infect or cause paralysis in mice. In contrast,
previous studies have found that when mice are exposed to viral samples shed by
people vaccinated with the standard Sabin oral polio vaccine, as many as 90
percent develop paralysis.
See:
Ming Te Yeh, Erika Bujaki, Patrick T. Dolan, Matthew Smith, Rahnuma Wahid, John
Konz, Amy J. Weiner, Ananda S. Bandyopadhyay, Pierre Van Damme, Ilse De Coster,
Hilde Revets, Andrew Macadam, Raul Andino. Engineering the Live-Attenuated
Polio Vaccine to Prevent Reversion to Virulence. Cell Host & Microbe, 2020;
DOI: 10.1016/j.chom.2020.04.003
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