Can a new vaccine halt the rising tide of vaccine-derived polio?

Public health experts hope a new vaccine, introduced in seven countries this year, will significantly reduce the incidence of polio cases in communities where children are not immunized and exposed to poor sanitation. But limited production is currently curtailing its reach. There are, essentially, two different categories of viruses that can cause polio. One is “wild” polio — the form of the virus believed to be in circulation for thousands of years. Its elimination is on the horizon, with cases now only found in Afghanistan and Pakistan. But the goal of eliminating polio in its entirety is complicated by a rise in cases of the “circulating vaccine-derived polioviruses,” or cVDPV. After a child is immunized through the oral poliovirus vaccine, remnants of the weakened poliovirus can leave the child’s body through feces, which can then enter the surrounding environment. Other children can then be exposed to the virus through contamination. And if population immunity is low and the virus is allowed to circulate, over time it can change into a form of the poliovirus that can cause paralysis. While cVDPV cases are rare, cases spiked last year as the COVID-19 pandemic halted vaccination campaigns. There were 1,107 cases recorded in 27 countries. In contrast, in 2016 there were only five cases in three countries and there has been a steady increase in cases each year with a large spike last year. This year, cases have gone down to 304 cases in 16 countries. Emergency listing Last year, many vaccination campaigns were put on hold because of movement restrictions, social distancing efforts, and health workers and community volunteers diverted to respond to the pandemic. “There are a lot of factors but the halting of the campaigns in March played the most significant role. We were having outbreaks [of circulating vaccine-derived polio viruses], at that particular time, and there was no response to these outbreaks,” said Dr. Pascal Mkanda, coordinator of World Health Organization’s polio eradication program in Africa. In November, the “type 2 novel oral polio vaccine,” or nOPV2 became the first vaccine to ever be listed by WHO’s for emergency use, which has since been granted to a handful of COVID-19 vaccines. It's a next generation version of the existing type 2 monovalent oral polio vaccine, which is specifically used in outbreak responses to cVDPV. This listing was granted because of the need to combat the rising cases of vaccine-derived poliovirus. Full licensure and WHO-prequalification of the vaccine is expected in 2023, said Simona Zipursky, co-chair of the nOPV2 Working Group and advisor to the director of polio eradication at WHO. “We are hopeful that we will get the green light to start using this vaccine on a wider scale,” Mkanda said. There are two other types of polio vaccines already in use: an injectable one — used primarily during routine immunization — and an oral one. A child that receives either vaccine will not get polio themselves. With the injectable vaccine, they won’t pass along the virus through the environment, because the vaccine is made with an inactivated virus. But if exposed to the wild virus in another way, it can still replicate in their gut and be excreted — risking continued circulation and the exposure of children who haven’t received the vaccine. In areas in high risk of polio, health workers administer the oral drops, which include a weakened form of the virus that generates antibodies and can be excreted. The danger of cVDPV arises when that weakened virus is allowed to circulate for an extended period of time in the environment and mutate into a paralytic form. If unimmunized children come into contact with that mutated form, they can become paralyzed. “It doesn't happen often, but when you're doing campaigns for 40 million children, even something that's rare will occur occasionally,” Zipursky said. If given both the injectable and the oral drops, a child has “optimal immunity against all strains of polio,” she said. Over the past decade, researchers have worked to alter these drops to make them more genetically stable, resulting in this new vaccine that reduces the chance the virus could mutate into a form that causes paralysis in low-immunity settings. “The risk isn't zero, but it's dramatically reduced,” Zipursky said. Roll out The Global Polio Eradication Initiative is working on the rollout of this vaccine, which started in March. Seven countries received the vaccine for free, including Benin, Congo, Liberia, Niger, Nigeria, Sierra Leone, and Tajikistan. They’ve administered about 70 million doses so far, with Nigeria administering 40 million of those. Under the emergency-use listing, only countries with or at high risk of outbreaks can use the vaccine. Countries also have to demonstrate they have good surveillance systems, Zipursky said, which includes collecting stool samples from children and sewage samples in areas where the vaccines are used, searching for the presence of polio. Surveillance officers also visit health centers, examining records for reported cases of paralysis. They also need safety monitoring systems in place to keep an eye on the children that received the vaccine — even though it has already been shown to be safe and effective in trials. Countries are expected to respond quickly with this new vaccine and reach over 90% of children in a given area, Zipursky said. “The risk isn't zero, but it's dramatically reduced.” --— Simona Zipursky, advisor to the director of polio eradication, WHO Countries that want to use this vaccine need to start preparing early to meet these criteria so there aren’t delays in responses when polio is detected, she said. Adding that some countries have struggled with managing quick responses. And the vaccine alone won’t solve the problem. There is still a need for improving sanitation, said Dr. Félicité Tchibindat, deputy regional director for West and Central Africa at UNICEF. “If there is poor sanitation, it's going to spread anyway,” Tchibindat said. And while the rollouts have so far been successful, there are some concerns around vaccine hesitancy, which has heightened as misinformation around the COVID-19 vaccines circulates on social media, impacting other vaccine efforts. “People are looking at vaccines in a different way,” Tchibindat said. “With COVID-19, we see a resurgence in resistance and a lot of questions about how these vaccines work, which we have not seen for many, many years.” “That battle is just starting,” she added. Limited supply The vaccine only has one producer — Bio Farma in Indonesia. And there are currently supply constraints, experts said. The pandemic has limited supplies because of the low availability of materials to produce the vaccines, as well as the limited number of people working at the manufacturing plant due to COVID-19 safety protocols, Zipursky said. The demand for the new vaccine has exceeded expectations, she said. New countries are interested in using the vaccine, and those that have already started using it want to use it more broadly. There is a technology transfer underway to teach another manufacturer in India to produce the vaccines. “However, given the COVID situation in India, some activities had to be delayed earlier this year, although they have now ramped up again. Technology transfers always take time, as the priority is to ensure the newly producing plant is able to maintain the same consistency and quality over time, as well as meet all the regulatory hurdles,” Zipursky said. The new manufacturer is expected to supply markets in 2023, she said, adding that with both manufacturers, there is an expectation that demand for nOPV2 will be met, but that also depends on the number of cVDPV cases. This makes work around surveillance and quickly identifying cases crucial, she said, “to identify the virus before it spreads too widely.” Having the vaccine eventually produced in Africa is also a goal, Tchibindat said, which could help reduce supply chain disruptions. There is, however, no shortage in supplies of the other polio vaccines, including monovalent oral polio vaccine type 2, which is also an effective tool at tackling outbreaks of circulating vaccine-derived polio virus. Zipursky said that even with the small risk of circulating vaccine-derived polio virus outbreaks that comes along with this vaccine, it's still a “great vaccine.” “Countries shouldn’t wait for more nOPV2 supply to become available and should respond quickly with available vaccines which have been proven safe and effective at stopping outbreaks,” she added. Visit the Building Back Health series for more coverage on how we can build back health systems that are more effective, equitable, and preventive. 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