New vaccines to foil polio’s last tricks

October 21, 2016 by Dr. John Konz and Hope Randall

PATH leader tells us why we need to invest in new vaccines to eradicate the disease.

A health worker administers an oral vaccine to an infant.

A health worker administers an oral vaccine to an infant. Photo: PATH/Doune Porter.

Editor’s note: The importance of polio vaccine coverage is an obvious lesson learned in global health. What is less obvious is why we’re investing in new vaccines if we’re already on the cusp of eradication. Guest contributor Hope Randall recently sat down to meet with John Konz, who leads a PATH project developing a new vaccine against the type 2 polio strain, called nOPV2. He explained why continued investment in this and other new vaccines is crucial for long-term protection and polio eradication.

Q: First of all, tell us a little bit about yourself. What drew you to PATH and to work on polio vaccine development?

Going back to graduate school, I knew that I wanted to focus on biotechnology. As I developed this interest, I realized that disease prevention through vaccines has so much more impact globally than treatment. From there, I was lucky enough to work in vaccine development at Merck for 17 years. Coming to PATH to develop new vaccines against polio was an opportunity to continue that long-term interest while being part of the broader polio eradication efforts. It’s likely a once-in-a-lifetime opportunity to potentially be able to say that I was part of eradicating a terrible disease.

Q: You are working on a new formulation of an oral polio vaccine (nOPV2) against the type 2 strain of polio. The world is so close to ending polio, and the wild-type 2 strain was declared eradicated in 2015, so why do we need a new vaccine for it?

The risks associated with type 2 polio will continue for some time from three sources: circulating vaccine-derived virus, which is still causing outbreaks; immunocompromised individuals who may continue to shed the virus for years; and the possibility that exposure or release could occur from ongoing laboratory activities or manufacturing.

Currently, the best tool to control type 2 outbreaks is the Sabin OPV2 stockpile; however, every use of this stockpile comes with the risk of seeding new outbreaks. A novel vaccine that has the benefits of Sabin OPV2 with reduced risks could be critical to complete eradication.

Q: Oral polio vaccine has been around for decades. What’s “novel,” or new, about nOPV2?

The original Sabin OPV strains were developed using an older method of attenuation which caused mutations that weakened the live virus while still ensuring the body’s immune response to the vaccine. At the time, the tools didn’t exist to understand what genomic changes caused the attenuation, nor whether those mutations were retained when the vaccine replicated after administration.

While Sabin OPV is generally quite safe, we now know that it can revert to a more virulent form in the human gut and on rare occasions cause disease in the recipient, the recipient’s contacts, or members of the community. Using new tools, a consortium of researchers can make more stable attenuating modifications that will make these nOPV2 strains less likely to revert than the Sabin strain. In principle, this should allow the vaccine to have the positive benefits of a replicating live viral vaccine with less risk of introducing vaccine-derived polio, which is crucial as we near eradication.

“We should keep improving tools to detect circulating polioviruses. We should seek safer, transmission-blocking vaccines. And consistent access to vaccines is crucial.”
— Dr. John Konz, director of PATH's novel oral polio vaccine project

Q: Where and how will the vaccine ultimately be used?

Assuming the program goes as planned, the primary goal is for the vaccine to replace Sabin OPV2 in the international emergency stockpile and be used for outbreak control.

Q: Given that there are two types of vaccines against polio, inactivated polio vaccine (IPV) and oral polio vaccine (OPV), why is OPV the vaccine of choice for controlling outbreaks?

IPV is a very good vaccine for preventing disease in the recipient, but it is not as good as the oral vaccine for preventing infection and transmission. In the case of outbreak control and eradication, breaking transmission chains is critical.

Q: First and foremost, the vaccine needs to be safe and effective. What are the other must-haves for this vaccine if it is going to be successful?

In addition to being generally safe, to differentiate this vaccine we need to be able to demonstrate that it is less likely to revert to a virulent form. Additionally, the vaccine will have to be able to be manufactured readily and, by extension, be affordable.

Q: In August 2016, the global community suffered a setback with the reappearance of wild polio in Nigeria after two years without a wild polio case. What are the lessons you took away from this news? How should it shape the way policymakers think about investments in global polio eradication?

Being new to the poliovirus vaccine community, I continue to be impressed by the resilience and commitment of everyone involved in the eradication efforts. I’m not sure that there is a new lesson here, but it does reinforce three concepts that the community already knows. We should keep improving tools to detect circulating polioviruses. We should seek safer, transmission-blocking vaccines. And—in this case most critically—consistent access to vaccines is crucial.

Q: Is PATH also working on polio vaccines for routine immunization?

Yes, PATH has a number of other collaborative efforts aimed at both improving IPVs and assisting manufacturers in various ways to build more global OPV and IPV production.

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