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    Building a new vaccine arsenal to eradicate polio    
      
     Date:   
         June 14, 2023   
     Source:   
         University of California - San Francisco   
     Summary:   
         Despite some of the most successful international vaccination   
         campaigns in history, the poliovirus continues to circulate around   
         the world, posing a threat of neurological damage and even paralysis   
         to anyone who is not vaccinated.   
      
      
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   FULL STORY   
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   Despite some of the most successful international vaccination campaigns   
   in history, the poliovirus continues to circulate around the world,   
   posing a threat of neurological damage and even paralysis to anyone who   
   is not vaccinated.   
      
   While the original polio strains, called wildtype, have largely been   
   eliminated, new strains can develop from the oral polio vaccine (OPV),   
   which is the one most used in the developing world. Oral vaccines   
   use live, weakened virus that occasionally mutates to an active form,   
   leading to outbreaks even in countries believed to have eliminated polio.   
      
   Scientists at UCSF and the UK's National Institute of Biological Standards   
   and Control (NIBSC) have developed two novel oral polio vaccines (nOPVs)   
   to bolster the World Health Organization's most recent push to finally   
   eradicate polio, which began two years ago using the first nOPV developed   
   by the same team.   
      
   These are the first new polio vaccines in 50 years.   
      
   Like the first nOPV, the two newest nOPVs, which were described in Nature   
   on June 14, are made from weakened poliovirus that has been genetically   
   engineered to reduce reversion to dangerous forms of the virus. The   
   development of these new vaccines was led jointly by Raul Andino, PhD,   
   UCSF professor of microbiology and immunology, and Andrew Macadam, PhD,   
   a virologist at NIBSC.   
      
   "With such variation in vaccination within and between countries,   
   poliovirus has persisted into the 21st century, with sometimes tragic   
   consequences," said Andino, co-senior author of the paper along with   
   Macadam. "We've designed these new vaccines using lessons learned from   
   many years of fighting polio and believe they will help eliminate the   
   disease once and for all."  The evolving battle against polio Polio is   
   insidious: it is usually asymptomatic, but can cause severe disability,   
   paralysis or death in about one in every hundred children. It spreads via   
   fecal or oral particles, so it is particularly problematic in regions with   
   poor sanitation. In the first half of the 20th century, polio outbreaks   
   routinely rolled through the US, leading to a race to develop vaccines.   
      
   The first effective polio vaccines emerged in the 1950s, kicking   
   off massive campaigns to immunize every person, with an emphasis on   
   children. The inactivated polio vaccine (IPV), made of dead poliovirus,   
   was given via injection, while the oral polio vaccine (OPV), made of   
   weakened poliovirus, was given on a sugar cube or in a candy. Today,   
   IPV is the vaccine of choice in countries with robust healthcare, and   
   OPV -- the cheaper, easier-to-administer option -- is used otherwise.   
      
   In populations where everyone is immunized early in life, it doesn't   
   matter whether they receive IPV or OPV, although these vaccines act   
   in different ways in the environment. People vaccinated with IPV can   
   still get infected with any polio that happens to be circulating. They   
   will not get sick, but they can silently transmit the virus to the   
   unvaccinated. People vaccinated with OPV can't silently transmit   
   circulating polio in this way, but they can shed the weakened virus they   
   were inoculated with and spread it to the unvaccinated. If the weakened   
   virus mutates, it can become pathogenic polio once more.   
      
   In populations with unvaccinated children -- whether due to refusal to   
   vaccinate, natural disaster, or war -- such vaccine-derived polio can   
   spread widely, causing severe disease in the unlucky few.   
      
   While the original, or "wildtype," poliovirus has only been recently   
   detected in Afghanistan and Pakistan, vaccine-derived polio has been   
   detected in countries as far flung as Syria, the Democratic Republic of   
   Congo, and the U.S.   
      
   In fact, there have been more cases of vaccine-derived polio than wildtype   
   in recent years, creating an urgency to counter this new source of polio.   
      
   In 2017, Andino and his colleagues discovered how OPV reverts to its   
   harmful form: a single mutation restores the virus's capacity to migrate   
   from the human gut and into the nervous system. Within a few years, the   
   group had devised a trio of mutations that make such genetic reversion   
   much less likely and packaged it into a new vaccine.   
      
   That vaccine, nOPV2, earned the WHO's first-ever emergency use listing   
   for a vaccine in 2020 and was quickly manufactured and distributed.   
      
   "Over 600 million doses were delivered to more than 28 countries, and   
   in ten instances it stopped ongoing outbreaks of vaccine-derived polio,"   
   said Andino.   
      
   "It gave us a lot more confidence that this actually was working as   
   anticipated."  Covering all the bases with polio eradication Despite   
   its effectiveness, nOPV2 only protects against one of three strains   
   of polio, and cases of polio have recently emerged in Israel, which is   
   heavily vaccinated, as well as in pockets of the US where people refuse   
   to vaccinate their kids.   
      
   Even where there are no polio cases in hospitals, polio continues to be   
   detected in wastewater in major cities. There may be 99% fewer polio   
   cases today than there were 30 years ago, but the last 1% has proven   
   hard to snuff out.   
      
   "If there's polio anywhere, it will come back where there are gaps in   
   vaccination," Andino said.   
      
   The latest work from Andino's group takes the solution they crafted   
   for nOPV2 - - the three mutations that usually prevent the vaccine from   
   becoming dangerous over time -- and engineers it into the other two types   
   of OPV. The resulting vaccines, nOPV1 and nOPV3, effectively prevented   
   polio in animal models. All three are much safer than the original OPVs,   
   which can occasionally cause paralysis in those who get the vaccine,   
   although this is rare (on the order of one case per two million children   
   vaccinated).   
      
   The two new vaccines are currently being tested in clinical trials to   
   ensure that they are both effective and do not revert to dangerous forms   
   in humans.   
      
   Andino is hopeful they will be incorporated into bivalent or trivalent   
   combinations with nOPV2. Children of the future will be equally protected   
   from polio for life, and perhaps the world will someday experience   
   decades in which zero polio is detected.   
      
   "The perception that polio is gone is a dangerous one," said Andino. "For   
   instance, just in India, 500,000 children are born each week, an enormous   
   number of susceptible people. We now have what we need to protect them."   
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Vaccines # Influenza # Infectious_Diseases #   
                   Mumps,_Measles,_Rubella # Cold_and_Flu # Bird_Flu #   
                   Viruses # Herpes   
       * RELATED_TERMS   
             o Vaccination o Mumps o Brain_damage o Rabies o H5N1 o Pain   
             o Face_transplant o Pathogen   
      
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   Story Source: Materials provided by   
   University_of_California_-_San_Francisco. Original written by Levi   
   Gadye. Note: Content may be edited for style and length.   
      
      
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   Journal Reference:   
      1. Ming Te Yeh, Matthew Smith, Sarah Carlyle, Jennifer   
      L. Konopka-Anstadt,   
         Cara C. Burns, John Konz, Raul Andino, Andrew Macadam. Genetic   
         stabilization of attenuated oral vaccines against poliovirus types   
         1 and 3. Nature, 2023; DOI: 10.1038/s41586-023-06212-3   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/06/230614220021.htm   
      
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