Friday, June 30, 2023

New forms of Oral Polio Virus


“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,” Andino says. “If there’s polio anywhere, it will come back where there are gaps in vaccination. The perception that polio is gone is a dangerous one.”

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To create the new vaccines, the researchers used the molecular backbone of their earlier vaccine for the type 2 virus. They retained the genetic components that help keep the weakened virus from becoming pathogenic. But they replaced coding regions for the virus capsid (shell) unique to the type 2 virus with sequences from the other two polio types.


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The oral polio vaccine is often used in resource-poor regions, due to its lower cost and easy delivery. The oral vaccine is also more effective in many ways, but it has a significant drawback: It is based on a live weakened poliovirus that can mutate and evolve. In rare cases, it can become infectious. This can lead to a vaccine-derived outbreak in communities with many unvaccinated people. There are three poliovirus types, with only type one still spreading in the wild. But episodes of all three types can still occur because of the vaccines.

Studies in mice showed that both novel vaccines triggered strong immune responses similar to those seen with the current oral vaccines. Each effectively prevented infection after exposure to the poliovirus. 


Since then, more than 600 million doses of the vaccine have been used to treat polio outbreaks in 28 countries. In their latest study, the researchers created modified oral vaccines that target the other two polioviruses, types 1 and 3. Research to develop the vaccines was supported in part by NIH. Results appeared in Nature on June 14, 2023.


Polio – a disease many have prematurely consigned to history – made headlines around the world in recent months when the virus was detected in relatively high-income country settings from New York, London, Montreal, and Jerusalem. This apparent comeback in polio-free countries has left many questioning the feasibility of eradication. On the contrary, we have never been closer to achieving our goal of a polio-free world: this resurgence only underscores the urgent need for eradication.

When the Global Polio Eradication Initiative (GPEI) was launched in 1988, nearly 1,000 children were being paralyzed with wild poliovirus (WPV) infection across 125 countries every single day. Since then, a concerted effort of health workers, communities, local governments, and global partners such as Rotary International has helped eradicate two of the three serotypes of wild poliovirus (WPV2 and WPV3) and cornered the remaining strain of WPV – type 1 (WPV1) – to small areas of Pakistan and Afghanistan – the last wild polio-endemic countries. The genetic diversity of the remaining chains of WPV1 is also on the decline, indicating the virus might very well be on the verge of being wiped out.  

However, this incredible progress is in jeopardy. Due in part to the COVID-19 pandemic, the world has seen a worrying drop in immunization rates over the past few years, creating pockets of under-immunized communities at heightened risk of polio infection and paralysis. Children missing polio vaccinations create opportunities for polio to re-emerge and spread – as seen in 2022 when WPV1 originating in Pakistan was detected in paralyzed children in Malawi and Mozambique. This episode served as a poignant reminder that as long as polio exists anywhere in the world, it remains a threat to people everywhere.

Persistently under-vaccinated communities are also at risk of outbreaks of vaccine-derived poliovirus (VDPVs). These polio variants evolve from oral polio vaccines (OPVs), which use a weakened form of the virus to protect children from infection and act as a key tool for many countries to stop the spread of polio. When a vaccinated child sheds that weakened virus into the environment, it can help provide indirect protection for the entire community. However, in areas with persistently low immunization coverage, the weakened vaccine virus can circulate over a prolonged period, ultimately regaining the ability to cause paralytic outbreaks that can spread across geographies. 

What do we do about it?

One technological solution to the VDPV situation is the development of OPV strains that are more genetically stable and therefore less likely to evolve into VDPVs. In 2011, a scientific consortium was formed to explore the development of a next-generation vaccine while still maintaining the advantages of existing OPV, such as ease of delivery and intestinal mucosal immunogenicity. As poliovirus serotype 2 strain has been associated with most of the paralytic polio outbreaks of cVDPVs, a new, type 2 OPV was selected as the initial focus of the consortium.

In November 2020, the novel oral polio vaccine type 2 (nOPV2) was authorized under the Emergency Use Listing (EUL) pathway by the World Health Organization (WHO) following positive findings from phase I and phase II studies of safety, reactogenicity, immunogenicity, and the desired genetic stability. The rollout of nOPV2 for outbreak response began in March 2021 and since then, more than 580 million doses of nOPV2 have been delivered in 28 countries, with surveillance data from initial field use indicating a high likelihood of success at closing outbreaks with a lower risk of seeding the emergence of new ones.

Regardless of which polio vaccine is used to stop an outbreak, there must be high immunization coverage for all children to be protected against paralysis. Following the detection of an environmental sample or confirmation of a case of paralytic polio, outbreak response campaigns must be launched in a timely manner to reach all at-risk communities with vaccines. Coordination transcending geographic borders is also key, which is why countries currently at a high risk of polio spread – such as Pakistan and Afghanistan as well as Malawi, Mozambique, Tanzania, Zambia, and Zimbabwe – are synchronizing campaigns to help ensure that underserved and migrant communities are not missed. Readiness on the regulatory front to use a vaccine under EUL provisions as in the case of nOPV2 and maintaining adequate global supplies of such vaccines will be important in minimizing the risk of the spread of polio.

https://pubmed.ncbi.nlm.nih.gov/25824845/

https://pubmed.ncbi.nlm.nih.gov/32330425/

https://pubmed.ncbi.nlm.nih.gov/37317297/

https://pubmed.ncbi.nlm.nih.gov/24175215/


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