Cutting-edge Science: Developing the First-ever Polio Protection for People with Immunodeficiency

For most people, protection against polio comes from a vaccine, but a select group of people are not protected by the vaccine. People with certain immunodeficiencies have no protection against paralytic polio. But that is hopefully about to change.

The Task Force’s Polio Antiviral Initiative is working with ViroDefense, Inc. which will soon initiate a clinical study to evaluate an antiviral combination that would be the first and only protection against paralytic polio for people with these immunodeficiencies. If the combination is well tolerated, it will be evaluated for efficacy in the target population. Assuming the combination is effective, safe and well tolerated, it could protect infected immunodeficient individuals and prevent the spread of the virus.

In the early 1950s, every country in the world had polio, an infectious disease that as recently as 1988 infected 350,000 people and paralyzed 1,000 children every day. However,  the development of vaccines has reduced polio by more than 99% since 1988, and public health teams have been closing in on eradication for the last decade. Two of three types of wild polio have now been eradicated and the remaining one (type 1 polio) is now endemic in just two countries: Afghanistan and Pakistan.

However, the last mile of the journey has been fraught with unforeseen challenges. New variations of poliovirus originating from the live oral vaccine have emerged and other diseases like COVID-19 have delayed polio eradication efforts due to lockdowns and diverting public health resources. 

“The vulnerable immune deficient group presents a significant challenge,” said Dr. Mark McKinlay, head of The Task Force’s vaccine portfolio and Director of the Polio Antivirals Initiative. “Solving this problem is a key component of the eradication effort. As long as poliovirus-excreting immune-deficient individuals remain unidentified they represent a risk for triggering an outbreak of paralytic disease in under-immunized communities.”

When the live oral polio vaccine is given to people with certain immunodeficiencies, their weakened immune systems can’t stop the replication of the virus in their gut. The virus can continue to replicate, often for years, and over time the virus can revert back to its paralytic form. At that point, the virus can cause paralysis in the individual and be released into the community either through waste water or person-to-person contact.

Therefore, current protocols prevent giving the live oral vaccine to people known to have one of the immunodeficiencies associated with prolonged virus excretion.

Research has identified two potent and virus-specific antiviral drug candidates – V-073 (referred to as pocapavir) and V-7404 – that each produce promising results to prevent infection and replication of poliovirus. Following the completion of the clinical safety studies, ViroDefense, Inc. will assess the effectiveness of the antiviral combination in stopping excretion of poliovirus in infected immune-deficient individuals.

One of the antivirals, pocapavir, is from a class of agents that McKinlay and his team at a previous job showed prevented death due to polio in mice in the 1980s. The compound inhibits the virus by preventing the uncoating or release of the infectious RNA from the virus capsid or outer shell.

“Just like a Rubik’s cube, if you stick a pin in it then you can’t turn it and open it, that’s exactly what the drug does to the virus. It prevents the virus from uncoating and releasing its RNA to start the replication process,” said McKinlay.

Antiviral mechanism explained

 
Watch Dr. McKinlay’s simple explanation of how a poliovirus antiviral works.

The safety trial of the combination is planned to begin soon. Simultaneously, the World Health Organization (WHO) and ministries of health are setting up surveillance systems, prioritizing countries that have been identified as having a higher risk of immunodeficiency, to identify individuals with the immunodeficiencies associated with prolonged excretion of poliovirus. If the combination antiviral therapy proves to be as effective as pocapavir was in the oral polio vaccine human challenge study, then once regulatory approval is granted countries would offer it to individuals identified as at-risk by the surveillance system.

This type of clinical trial builds on The Task Force’s expertise in conducting clinical trials, such as the LEDoxy Trials, currently underway in five countries to assess the effectiveness of the drug doxycycline to reduce acute attacks and inflammation for people suffering from lymphedema, more commonly known as elephantiasis, caused by lymphatic filariasis. The results will be published early next year.

Building on this expertise, the Polio Antivirals Initiative convenes partners to review the antiviral development and plan for product registration. The collaboration includes the antiviral research and development company ViroDefense, Inc. that develops, manufactures and ultimately will deliver the combination, as well as polio experts from the Bill & Melinda Gates Foundation, WHO, U.S. Centers for Disease Control and Prevention, and Rotary International who provide input into the development, registration and use of the combination.

Header photo: Dr. Sanam Hussain, Pakistan Field Epidemiology and Laboratory Training Program (FELTP) alumni, checks polio immunization status of children among the Murri Huts nomadic communities of UC Sonwalhar-I of Taluka Kotri, a rural area on the border of District Jamshoro and District Thatta of Sindh Province. Photo courtesy of Pakistan FELTP.

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