How a six-in-one vaccine could soon help the world get rid of polio for good

Polio eradication is a delicate dance. And one of the biggest challenges facing the people trying to choreograph its final steps is how to phase out use of oral polio vaccines.

The oral vaccines have brought the paralyzing viruses to the brink of  annihilation; so far this year there have only been six cases detected, five in Afghanistan and one in Pakistan. But a feature of the oral vaccines — that the live viruses in them can spread and on rare occasions regain the power to paralyze — means that while they are in use, the world will never be free of polio.

A decision that will be made next week may make it easier to take the final steps of the eradication endgame. The governing board of Gavi, the Vaccine Alliance is expected to approve a new vaccine that would increase the number of children around the world who are protected against the worst of what polioviruses can do, in the process making the eventual withdrawal of oral polio vaccines less dangerous.

The Gavi board will vote on a proposal to offer the countries it helps a combination product that includes inactivated polio vaccine. IPV, as it is known, does not contain live viruses and cannot create the problem seen with the oral vaccines.

The United States has used IPV exclusively since 2000, and Gavi has been helping qualifying countries to buy IPV since 2013. But this would be the first time it would offer assistance in purchasing polio vaccine in a combination format that would protect children against hepatitis B, Haemophilus influenzae, diphtheria, tetanus, pertussis and all three types of polioviruses.  It will be a six-in-one vaccine, a hexavalent in the vernacular of vaccines.

Roland Sutter, who has been working on polio eradication for decades, thinks this will be an important step. The addition of this six-in-one vaccine to Gavi’s portfolio “is probably the best thing … since sliced bread,” he told STAT.

If approved by the Gavi board, the vaccine could start to become available to countries that choose to use it next year.

There are multiple advantages to this approach, chief among them the fact that this program could increase the number of children around the world who are routinely getting IPV to protect them from polio. An important bonus: It would help to ensure countries don’t stop vaccinating against polio too quickly, if and when victory over polio is declared.

“It reduces the risk that countries would discontinue IPV once we’re at a post-eradication period, because it would be built in,” said Aurélia Nguyen, Gavi’s chief program strategy officer.

By bringing together Gavi’s existing five-in-one or pentavalent vaccine and IPV, “we’re actually strengthening both programs,” Nguyen said.

Gavi expects some countries will continue to use the five-in-one vaccine — which protects against the same diseases, minus polio — and give IPV separately. But a number are expected to adopt the new product; UNICEF, the UN’s Children Fund, estimated last year that the market for the hexavalent vaccine will be 100 million doses a year by 2030.

The vaccine would be given in three doses early in life — at six, 10, and 14 weeks — with a booster shot given at some point between the child’s first and second birthday.

Currently countries that access vaccines through Gavi’s program give three doses of pentavalent and two doses of IPV independently. (Two doses of IPV is recommended, but some countries only give one.)

Combination vaccines are more expensive, and adding a component raises the cost. But Gavi and its partners have been negotiating with manufacturers, who know there will be a big demand if they produce a hexavalent for the right price. Nguyen said Gavi expects three producers to be in a position to supply hexavalent vaccine between now and 2026, with another two — including one from Africa — slated to come onboard in 2027.

The per-dose cost of the hexavalent may be higher, but there will be modest savings elsewhere due to fewer doses needed. For Gavi, which not only provides support for vaccines but for the equipment needed to turn vaccines into vaccinations, that means fewer syringes and fewer sharps disposal boxes, Nguyen said. For countries, fewer injections mean savings on the refrigerators and coolers needed to keep vaccines at safe storage temperatures. It also means fewer vaccination sessions per child, freeing up precious time for health workers.

“This is very much the crux of the discussion that we’re bringing to our board this month, which is to say there is an incremental cost to Gavi and to countries,” she said. “However, those are offset by the extra health impact, the saved ancillary and time costs and the programmatic improvements, as well as incentivization of innovation for manufacturers. We believe that on balance, this is worth it.”

So does Sutter, who now works as a consultant after years at the World Health Organization, and before that at the Centers for Disease Control and Prevention.

“High hexavalent coverage, in my way of thinking, would greatly increase immunity to polioviruses,” he said in an email. “That would help facilitate eradication, and would help maintain eradication.”

Sutter said the sharp increase in vaccine-derived polio cases since 2016 has made plain the need to build up immunity. That’s when the polio eradication program withdrew one component of the oral polio vaccine, the part that protected against now extinct type 2 polioviruses, in an operation known as “the switch.”

A bit of background on oral polio vaccines is crucial here. The vaccines that Albert Sabin designed contain live but weakened polio viruses. Children are given these vaccines in liquid form — two drops dripped into open mouths from an eye dropper.

Children who receive Sabin vaccines excrete live viruses in their stools. In countries where hand hygiene and water sanitation is poor, these vaccine viruses can transmit to unimmunized children, passively vaccinating them in the process. But if they spread long enough, the viruses can regain the power to paralyze, setting off transmission chains that act like wild polio. Last year, 30 children globally were paralyzed by wild polio viruses, while 865 children were paralyzed by vaccine viruses.

In 2016, the Global Polio Eradication Initiative dropped the type 2 polio component from the oral vaccine in what was meant to be a globally synchronized effort. Type 2 wild viruses had been eradicated, and declining polio vaccine coverage in some parts of the world was actually spurring development of type 2 vaccine virus transmission chains. Removing the component from the vaccine would prevent creation of more vaccine viruses, the thinking went.

The idea was well intentioned, but the execution was poor. Countries were meant to build up polio immunity before the switch by giving children a dose of the inactivated vaccine, but that didn’t happen everywhere. There were global shortages of IPV and ineffective vaccination efforts in some countries. That led to a plunge in immunity to type 2 polio in some parts of the world — creating fertile ground for the type 2 vaccine viruses that were spreading.

In the years since the switch, researchers funded by the Bill and Melinda Gates Foundation have rushed to create an alternative oral polio vaccine — known as novel or nOPV — which has proven to be much safer; it regains the power to paralyze far less frequently. A version of this vaccine targeting type 2 viruses is in use; new oral vaccines targeting type 3 viruses (which have also been eradicated) and type 1 viruses are in clinical testing.

But even these oral vaccines will need to be withdrawn eventually. Building up immunity with the hexavalent vaccine will help to lay the groundwork for that day, Sutter suggested.

“If you get good coverage with this — let’s say you get 90% coverage, real coverage — then you probably don’t need the oral vaccine anymore,” he said.

IPV prevents children from being paralyzed, but it does not prevent infection with polio viruses, because it doesn’t confer immunity in the gut, where the viruses attack. The only way to stop transmission of wild polio — or  vaccine viruses — is by using the oral vaccines judiciously, building up enough immunity that they don’t find children to infect, and then stopping use of the oral vaccines while buttressing immunity with IPV.

Of course, the fundamental problem of the polio eradication initiative is that too few children globally are vaccinated against polio. Experts hope that the somewhat higher coverage rates seen with the pentavalent vaccine will translate into more children getting some polio protection when the hexavalent vaccine — if approved — is rolled out.

In Sutter’s ideal world, the hexavalent vaccine gets approved and is put into use in conjunction with a trivalent vaccine combining the three novel oral polio vaccines. With decent coverage, he said “you probably would massively decrease the geographic areas where you would have to do [polio vaccination] campaigns,” he said. “That possibly could be one path to eradication. Slow but not very risky.”

Not risky, but definitely more expensive. Kimberly Thompson, a mathematical modeler who has worked on polio eradication for decades, agreed with Sutter that the hexavalent is an important option, given the state of the eradication effort. Polio eradication was meant to be completed by 2000, in time for the dawn of the new millennium. Twenty-three years later, it struggles on.

Thompson bemoaned that earlier missteps in the polio program have made this option necessary, noting that the original promise of polio eradication — that countries could one day stop vaccinating against polio and use the money for other needs — is fading from view.

“The move towards just an expectation of long-term commitment to these expensive IPV vaccines is just basically blowing away the whole idea that polio eradication would be cost saving,” said Thompson, president of the nonprofit group Kid Risk.

“The polio program is just getting more expensive with time.”