In Victory Against Polio, Hope for the Battle Against COVID-19 - University of Virginia

Posted: 13 May 2020 01:40 PM PDT

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For much of the 20th century, summer was "polio season," and people were accustomed to seeing swimming pools and movie theaters closed to stave off the latest epidemic. Shaking hands was off limits, and even touching money was thought perilous. The ever-present threat of death or permanent paralysis from polio was part of life, as were regular social-distancing efforts to limit the terrible disease's spread.

For many younger people in America, the idea of living under threat from a such a serious infectious disease has been hard to imagine, at least until COVID-19. But now the story of the victory over polio is even more resonant. In a new editorial in the journal Science, UVA Health's Dr. William A. Petri and graduate student Alexandra N. Donlan highlight medicine's great triumph over polio, at least in the West, and hold out hope we can do the same for COVID-19.

"Nearly seven decades ago the United States was faced with a similar challenge: the race to develop a vaccine against an infectious disease," said Petri, an infectious disease expert who is developing a COVID vaccine. "Jonas Salk's demonstration of the ability of vaccination to prevent paralysis due to polio in 1955 led to a nationwide celebration and Salk's invitation to the White House."

Preventing Polio

The editorial authors call the prevention of polio epidemics a "signature success of science in the 20th century." But it was no easy task, they note, and the worldwide eradication of polio remains elusive.

Salk first developed an injectable vaccine in the mid-1950s. It was then tested in 2 million children in what Petri and Donlan call a "herculean" effort. "Today," they write, "the faith in, and support of, scientific research by the American public is, arguably, founded on the polio vaccine."

The Oral Vaccine

An oral vaccine soon followed, developed by Albert Sabin, and the two vaccines have served as the armament for vanquishing polio around the world. There is a drawback to the oral vaccine, however: Because it is manufactured using live, but weakened, virus, recipients excrete live virus in their stool. This can lead to disease transmission in communities with low vaccination rates, especially in areas with limited sanitation infrastructure. There are also, rarely, cases of the weakened virus taking sufficient hold in a vaccine recipient to allow person-to-person transmission. This has resulted in polio outbreaks in recent years in Africa and parts of Asia. To overcome this, the Bill & Melinda Gates Foundation is supporting the fast-tracking of clinical trials of a new version of the oral vaccine, much as scientists are fast-tracking potential vaccines for COVID-19.

While more work remains to be done to eradicate polio around the world, the disease's conquest in the West speaks to the tremendous power of vaccine research. Polio, in America, stands alongside measles, mumps, tetanus, smallpox and more as serious diseases that are no longer a serious threat. Researchers hope, in the not-too-distant future, COVID-19 will join that list.

"As the world faces COVID-19," the scientists conclude, "it is heartening to see the same application of science to public health for [COVID] as the one used for the last 70 years of polio-virus research."

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'Designer virus' is first new oral polio vaccine in 50 years: Phase 1 trial shows promise for completion of stalled eradication effort; offers lessons for COVID-19 vaccine development - Science Daily

Posted: 23 Apr 2020 12:00 AM PDT

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, published April 23, 2020 in Cell Host and Microbe, 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.

"To my knowledge, this is the first effort to rationally design a live attenuated virus based on detailed understanding on its biology, as opposed to the standard approach of blindly passaging the virus in animal cells to eliminate human virulence through poorly understood mechanisms," said Andino, a professor of microbiology and immunology at UCSF.

The new study presents results of a double blinded phase 1 clinical trial conducted in 15 adult volunteers at the University of Antwerp, all of whom had previously been vaccinated with an inactive vaccine composed of shredded virus particles to ensure they could not be made sick by the live vaccine.

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.

A phase 2 trial is currently underway and shows promise, Andino said, and the WHO is planning a phase 3 trial, hoping to fast-track development of the vaccine as an emergency measure to contain these outbreaks of vaccine-derived polio.

Applying Polio's Lessons to Search for COVID-19 Vaccine

In the wake of the suspension of the WHO's polio eradication efforts during the COVID-19 crisis, Andino's lab is now applying all they've learned designing polio vaccines to the search for new approaches for a SARS-CoV-2 vaccine, including developing a mouse model to better understand exactly how the virus spreads and causes disease.

Dozens of other COVID-19 vaccine efforts are going after the low-hanging fruit of traditional vaccination using isolated viral particles or more advanced RNA-based vaccination, but Andino is working to understand the biological pathways within the virus that might be most amenable to transformation into a safe but effective live attenuated vaccine that could be rapidly produced for worldwide distribution.

"I believe the lesson of polio is that it will take time to develop an optimal vaccine against SARS-CoV-2, and early efforts are likely to meet with unexpected challenges," Andino said. "Once we do have safe and effective vaccines, they'll need to be produced at global scale, which will probably require the use of older technologies that are already in place. Given how little we know about this new coronavirus, I'm betting we'll need all the weapons we can muster."

Authors: Ming Te Yeh of UCSF was the study's lead author. Macadam and Andino are co-corresponding authors. Additional authors on the paper were Patrick T. Dolan of UCSF; Erika Bujaki and Matthew Smith of the National Institute for Biological Standards and Control in the UK; Rahnuma Wahid, and John Konz of the Center for Vaccine Innovation and Access in Seattle; Amy J. Weiner and Ananda S. Bandyopadhyay, of the Bill and Melinda Gates Foundation in Seattle; and Pierre Van Damme, Ilse De Coster and Hilde Revets of the Centre for the Evaluation of Vaccination at the University of Antwerp.

Funding: This work was supported in part by National Institutes of Health (NIH R01 AI36178, AI40085, P01 AI091575), the UK Department of Health Policy Research Programme (NIBSC Regulatory Science Research Unit, 044/0069) and the Bill and Melinda Gates Foundation.

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