{"id":741,"date":"2020-04-24T11:14:52","date_gmt":"2020-04-24T05:44:52","guid":{"rendered":"http:\/\/www.potentialloops.org\/?p=741"},"modified":"2020-04-24T11:14:54","modified_gmt":"2020-04-24T05:44:54","slug":"designer-virus-is-first-new-oral-polio-vaccine-in-50-years","status":"publish","type":"post","link":"https:\/\/www.potentialloops.org\/?p=741","title":{"rendered":"Designer virus’ is first new oral polio vaccine in 50 years"},"content":{"rendered":"\n

Phase 1 trial shows promise for completion of stalled eradication effort; offers lessons for COVID-19 vaccine development <\/h4>\n\n\n\n

Date: April 23, 2020 <\/p>\n\n\n\n

Source 1: University of California – San Francisco<\/p>\n\n\n\n

Source 2: www.sciencedaily.com <\/a><\/p>\n\n\n\n

Summary: 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. <\/p>\n\n\n\n

\"\"
Poliovirus illustration (stock image).
Credit: \u00a9 Kateryna_Kon \/ Adobe Stock<\/a><\/em> ,Sciencedaily.com<\/figcaption><\/figure>\n\n\n\n

Before being halted due to the COVID-19 \npandemic, a relentless vaccination campaign had nearly succeeded in \neradicating polio from the world. Between 2000 and 2017, the World \nHealth Organization (WHO) estimated that its campaign had reduced the \nburden of the disease by 99 percent, preventing more than 13 million \nchildren from becoming infected and risking potentially debilitating \nparalysis.<\/p>\n\n\n\n

But in recent years, the eradication effort has been plagued by \noutbreaks of vaccine-derived polio — in which the weakened virus used \nin oral polio vaccines evolved the ability to escape from vaccinated \nindividuals and spread in communities with poor vaccination rates.<\/p>\n\n\n\n

Now, with support from the Bill and Melinda Gates Foundation, UC San \nFrancisco virologist Raul Andino, PhD and Andrew Macadam, PhD, of the \nUK’s National Institute for Biological Standards and Control (NIBSC) \nreport promising Phase 1 clinical results for the first new oral polio \nvaccine in 50 years, which they have designed to be incapable of \nevolving the ability to cause disease in humans.<\/p>\n\n\n\n

In a 2017 study, Andino and colleagues discovered that in every \nvaccine-derived polio outbreak they studied, the virus had used the same\n three evolutionary steps to mutate from harmless vaccine into a \nregional menace.<\/p>\n\n\n\n

In their new study, published April 23, 2020 in Cell Host and Microbe<\/em>,\n Andino, Macadam, and colleagues at the Gates Foundation, the Center for\n Vaccine Innovation and Access in Seattle, and the Centre for the \nEvaluation of Vaccination at the University of Antwerp have employed \nclever genetic wizardry based on decades of study of the poliovirus’s \nbiology to redesign the vaccine to ensure that is incapable of following\n this three-step pathway to re-evolve virulence. Specifically, they \nstabilized a region of the viral genome that is required for it to \nre-evolve the ability to infect humans, and ensured that the virus could\n not get rid of this modification even by exchanging genetic material \nwith related viruses.<\/p>\n\n\n\n

“To my knowledge, this is the first effort to rationally design a \nlive attenuated virus based on detailed understanding on its biology, as\n opposed to the standard approach of blindly passaging the virus in \nanimal cells to eliminate human virulence through poorly understood \nmechanisms,” said Andino, a professor of microbiology and immunology at \nUCSF.<\/p>\n\n\n\n

The new study presents results of a double blinded phase 1 clinical \ntrial conducted in 15 adult volunteers at the University of Antwerp, all\n of whom had previously been vaccinated with an inactive vaccine \ncomposed of shredded virus particles to ensure they could not be made \nsick by the live vaccine.<\/p>\n\n\n\n

The trial found that the new designer polio vaccine was both more \nstable and more effective than the 50-year old Sabin vaccine from which \nit was derived. Specifically, the new vaccine caused participants to \ngenerate plentiful antibodies against the poliovirus, and despite \nshedding viral particles in their stool, those particles were unable to \ninfect or cause paralysis in mice. In contrast, previous studies have \nfound that when mice are exposed to viral samples shed by people \nvaccinated with the standard Sabin oral polio vaccine, as many as 90 \npercent develop paralysis.<\/p>\n\n\n\n

A phase 2 trial is currently underway and shows promise, Andino said,\n and the WHO is planning a phase 3 trial, hoping to fast-track \ndevelopment of the vaccine as an emergency measure to contain these \noutbreaks of vaccine-derived polio.<\/p>\n\n\n\n

Applying Polio’s Lessons to Search for COVID-19 Vaccine<\/strong><\/p>\n\n\n\n

In the wake of the suspension of the WHO’s polio eradication efforts \nduring the COVID-19 crisis, Andino’s lab is now applying all they’ve \nlearned designing polio vaccines to the search for new approaches for a \nSARS-CoV-2 vaccine, including developing a mouse model to better \nunderstand exactly how the virus spreads and causes disease.<\/p>\n\n\n\n

Dozens of other COVID-19 vaccine efforts are going after the \nlow-hanging fruit of traditional vaccination using isolated viral \nparticles or more advanced RNA-based vaccination, but Andino is working \nto understand the biological pathways within the virus that might be \nmost amenable to transformation into a safe but effective live \nattenuated vaccine that could be rapidly produced for worldwide \ndistribution.<\/p>\n\n\n\n

“I believe the lesson of polio is that it will take time to develop \nan optimal vaccine against SARS-CoV-2, and early efforts are likely to \nmeet with unexpected challenges,” Andino said. “Once we do have safe and\n effective vaccines, they’ll need to be produced at global scale, which \nwill probably require the use of older technologies that are already in \nplace. Given how little we know about this new coronavirus, I’m betting \nwe’ll need all the weapons we can muster.”<\/p>\n\n\n\n

Authors: Ming Te Yeh of UCSF was the study’s lead author. Macadam and\n Andino are co-corresponding authors. Additional authors on the paper \nwere Patrick T. Dolan of UCSF; Erika Bujaki and Matthew Smith of the \nNational Institute for Biological Standards and Control in the UK; \nRahnuma Wahid, and John Konz of the Center for Vaccine Innovation and \nAccess in Seattle; Amy J. Weiner and Ananda S. Bandyopadhyay, of the \nBill and Melinda Gates Foundation in Seattle; and Pierre Van Damme, Ilse\n De Coster and Hilde Revets of the Centre for the Evaluation of \nVaccination at the University of Antwerp.<\/p>\n\n\n\n

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.<\/p>\n\n\n\n

Story Source:<\/strong><\/p>\n\n\n\n

Materials<\/a> provided by University of California – San Francisco<\/strong><\/a>. Original written by Nicholas Weiler. Note: Content may be edited for style and length.<\/em><\/p>\n\n\n\n

www.sciencedaily.com<\/a><\/p>\n\n\n\n

\n\n\n\n

Journal Reference<\/strong>:<\/p>\n\n\n\n

  1. Ming Te Yeh, Erika Bujaki, Patrick T. Dolan, Matthew Smith, Rahnuma \nWahid, John Konz, Amy J. Weiner, Ananda S. Bandyopadhyay, Pierre Van \nDamme, Ilse De Coster, Hilde Revets, Andrew Macadam, Raul Andino. Engineering the Live-Attenuated Polio Vaccine to Prevent Reversion to Virulence<\/strong>. Cell Host & Microbe<\/em>, 2020; DOI: 10.1016\/j.chom.2020.04.003<\/a>\n<\/li><\/ol>\n\n\n\n
    \n","protected":false},"excerpt":{"rendered":"

    Phase 1 trial shows promise for completion of stalled eradication effort; offers lessons for COVID-19 vaccine development Date: April 23, 2020 Source 1: University of California – San Francisco Source 2: www.sciencedaily.com Summary: Virologists report promising Phase 1 clinical results for the first new oral polio vaccine in 50 years, which they have designed to 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