When top US health authorities convened in late January to brief President Barack Obama on the Zika outbreak in Latin America, the post-meeting scuttlebutt was that the president was eager to push development of a Zika vaccine.
The officials attending the meeting tried to convey an inconvenient reality: Real-world need and vaccine development speed are rarely in sync. Vaccines take years to produce, test, and license. The Zika virus, which had received scant study before 2016, was unlikely to prove to be an exception to that truth.
And yet a mere 10 months later, despite funding delays from a fractious pre-election Congress, three experimental Zika vaccines are already being tested in people; another four or five should start human trials between now and next fall. Larger Phase 2 trials for several candidate vaccines are planned for 2017; one will begin within the next couple of months.
Let’s be clear: That is warp speed for vaccine development, especially in a case, such as this, where the race commenced from a standing start. But will there be a market for a Zika vaccine when the work is done? That question hangs over this work.
The impressive progress so far underscores what scientists have predicted: The Zika virus is not a difficult target, from a vaccine design point of view.
But even with an easy mark, vaccine production takes time. So even though one vaccine, from Inovio Pharmaceuticals, went from green light to serum injected into arms in a record-breaking eight months, the current best-case scenario suggests an emergency-use Zika vaccine might be available a couple of years from now.
“Our goal is to have enough data around some of these vaccine candidates by the end of 2018 that there could be a discussion on consideration for using it in the current outbreak,” explained Dr. Rick Bright, who runs a government program that spurs development of vaccines, drugs, and tests needed to respond to biological threats.
“The second part of our government goal is to have a Zika vaccine that’s fully licensed to the marketplace by the end of 2020.’’
Bright is director of the Biomedical Advanced Research and Development Authority, an office in the Department of Health and Human Services. BARDA is currently funding five projects, including work by Moderna (MRNA) Therapeutics and Takeda (TAK) Pharmaceuticals’s vaccines division, both based in Cambridge, Mass., and Emergent Biosolutions (EBS), of Gaithersburg, Md. It is also helping to fund a collaboration between the National Institutes of Health and Butantan — a Brazilian government-funded institute that is the largest vaccine producer in Latin America — on a combination dengue and Zika vaccine.
From where Bright sits, Zika will be a long-term problem, so the work is going well. “Things are moving forward. Very, very nicely actually.”
So far no red flags have been raised on the safety side, though only a few hundred people in total have received a Zika vaccine.
It’s still too soon to say how effective the experimental vaccines are, though the expectations are that a number will be successful. Vaccines to protect against a couple of related viruses, yellow fever and Japanese encephalitis, are highly effective.
Questions also remain about how many doses each person would need to be protected, and how long protection would last. The aim is to produce something that safeguards women — and men who might infect them through sexual transmission of the virus — for the duration of their childbearing years.
But the biggest question — and it haunts this work — relates to how much demand there will be for a Zika vaccine by the time one or several of these candidates makes it through the three rounds of human testing and wins market approval from the Food and Drug Administration.
“That’s something we talk about a lot,’’ admitted Jon Heinrichs, associate vice president and project lead for Sanofi (SNY) Pasteur, the only pharmaceutical giant with hopes of producing a Zika vaccine in the near term. (GlaxoSmithKline is also working on a Zika vaccine, but it is using a new vaccine approach and is several years away from human testing.) “We have models that suggest there is no profitability for this vaccine, and we have models that suggest it could be profitable. Time will tell.”
Heinrichs said Sanofi is already gearing up to produce the vaccine, a step manufacturers don’t generally take this early in a development project. After all, the vaccine — designed and being tested by scientists at the Walter Reed Army Institute of Research in Bethesda, Md. — hasn’t yet been shown to protect people. The first test of this vaccine in people began only four weeks ago.
As things currently stand, the initial Zika panic triggered by pictures of Brazilian babies born with tiny, misshaped heads has tempered in some quarters. Early estimates of upwards of 6,000 affected infants in one part of the country alone have been downgraded to about a third of that number. Other countries have reported affected pregnancies, but so far the numbers remain low. Still, some affected pregnancies have yet to come to term.
And no one knows what to expect from the virus, in large measure because no one knows how much circulation of Zika there has been in the past in other parts of the world.
One theory suggests the virus spreads frequently in parts of Asia and Africa, infecting most people when they are children and leaving women immune by the time they start to have babies. If that’s true, the problem of Zika birth defects may become very rare once that pattern is established in Latin America, the thinking goes.
Persuading people to buy a vaccine to protect against something they don’t see as a threat is a tough proposition.
“The problem … is we don’t really understand the epidemiology of the virus,” said Heinrichs. That makes it impossible, he said, to generate good estimates of the potential demand for the market. “Will the market include Latin America, Asia, Africa, and potential for the US and Europe? Or will be limited to stockpiling in case of future epidemics?”
Even Bright acknowledged it isn’t clear if a Zika vaccine will become part of the schedule of vaccines given in childhood, or is marketed to people traveling to places where Zika spreads.
But the reality is that if the world is going to have a Zika vaccine, the scientific and pharmaceutical communities can’t wait to get a better gauge on the need, said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.
Scientists at Fauci’s institute designed a Zika vaccine using a pattern they developed for a West Nile virus vaccine about a decade ago. The West Nile vaccine worked well, but was never brought to market because vaccine manufacturers didn’t think it would sell.
The NIAID Zika vaccine has gone through the first round of human testing and will move to a Phase 2 trial in the first quarter of 2017. So far no manufacturer has licensed it, but Fauci predicted a commercial partner will come forward if the testing shows the vaccine works.
Fauci doesn’t think the Zika vaccine will suffer the same fate as the West Nile product, suggesting the development of a vaccine to protect against rubella is a more likely model in this situation.
Rubella — sometimes called German measles — was a childhood disease that caused relatively minor illness in kids. When it infected women who were pregnant, however, devastating birth defects occurred in their offspring. In the last major rubella outbreak in the United States — in the mid-1960s — an estimated 20,000 affected babies were born deaf, blind, or with mental disability.
The rubella vaccine, which was licensed in 1969, was brought to market to prevent infections during pregnancy. And that’s the goal for a Zika vaccine.
But there will need to be substantial funding — government funding — if that is to happen. How much is unclear but there are some clues. BARDA has already committed $43 million for the Phase 2 trial for the vaccine Sanofi Pasteur has licensed.
The much larger Phase 3 trials needed to prove that a vaccine works typically cost hundreds of millions of dollars apiece. “That’s really where the big costs are going to be,” said Heinrichs, who said Sanofi is in talks with BARDA about additional financing for its Phase 3 trial.
It’s anyone’s guess how eager the new administration will be to proceed with this work.
But Terry Ragon, a business tycoon who started a Boston-based research institute, said the government should continue to fund the pursuit of a Zika vaccine.
Some Harvard scientists supported by his Ragon Institute have designed a Zika candidate vaccine — though it hasn’t attracted a commercial partner either.
Ragon has talked with pharmaceutical industry leaders about Zika, and he understands they have a responsibility to shareholders to make profits. He doesn’t fault them for hesitating given the uncertainty.
“Clinical trials are really expensive. And so the barrier to getting a commercial entity to take this one is just too high,” said Ragon, who suggested if the government absorbs these costs, a Zika vaccine might be commercially viable.
“But the point is there needs to be a partnership where there are certain diseases that are deemed so horrible that we cannot allow them to happen or continue.”