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the public domain this time. “We’re privately owned, we have shareholder responsibility, we can’t just go off and do stuff for free for others,” says Gerngross.
The aim this time would be to license the antibodies to a drug developer to create a treatment for those already infected with Zika.
“Laura’s team has demonstrated that within six weeks they can isolate antibodies that are highly neutralizing,” says Gerngross. “If you want to put in place a rapid response system [to emerging viral threats], there’s no more excuses.” [Due to an editing error, this quote previously misstated the amount of time taken to isolate antibodies.]
To be clear, once a developer has a handful of powerful, promising antibodies, the “rapid response” gives way to traditional development timelines and procedures. Drug makers have to modify the antibodies, test them in animals, get their manufacturing in place, and check several other boxes. In the gravest emergencies, certain strictures can be circumvented. In the 2014 Ebola outbreak in West Africa, at least seven infected people received the drug ZMapp, made by Mapp Biopharmaceutical of San Diego, even though it had never gone through a day of human testing.
As NIAID and many other groups have announced, several Zika vaccine programs are also underway. Vaccine and drug development are very different processes, but vaccine makers are also looking for short cuts and head starts. One of the world’s biggest, Sanofi, has already commercialized vaccines against dengue (Dengvaxia), yellow fever (VF-VAX) and Japanese encephalitis (Imojev), all Flaviviruses. It announced in February it would start on a Zika vaccine. Nicholas Jackson, head of global research at the Sanofi Pasteur vaccine group, told Fortune this month that Sanofi plans to use the same “backbone” from its other vaccines, which could help assuage safety questions.
I asked for further explanation of what Sanofi has learned from its other Flavivirus projects to move its Zika vaccine quickly. Spokeswoman Susan Watkins kept the descriptions vague: “Our available vaccine technology… and established Flavivirus collaborative network are strong assets with the capacity to potentially accelerate our R&D efforts to find a vaccine against Zika.” She also said Sanofi hopes to start clinical testing in the second half of 2017. [Update: Watkins wrote back to point out that Sanofi has used this process successfully before. It built its Japanese encephalitis and dengue vaccines on a “backbone” taken from its yellow fever vaccine, replacing key yellow fever genes with corresponding genes from the other viruses.]
One private company with a more ambitious timeline is PaxVax, of Redwood City, CA. The company, with funding from private equity and public health groups, has a typhoid vaccine on the market that it acquired two years ago and could see FDA approval of its cholera vaccine in June.
For Zika, the company’s starting point is an empty shell of the virus with no genetic material, forming so-called “virus-like particles” that resemble the virus’s structure but cannot cause an infection.
PaxVax is basing the work on its previously undisclosed development of a dengue vaccine, not as a product but as a “proof of concept” to show that the company’s VLP technology can simulate a Flavivirus. The Zika vaccine uses techniques from that project, says CEO Nima Farzan, and could be ready for human trials before the end of 2016 if regulators allow.
Before a drug or vaccine can come to market, there are formidable scientific and regulatory hurdles. While the family ties between Zika, dengue, and other Flaviviruses could provide clues and stepping stones, they could also end up as a hindrance. Could a person’s previous dengue infection make a Zika infection worse? Nothing has been proven, but researchers are suspicious that Zika became a big threat only when it emerged in a region where dengue is common. “It’s a huge concern,” says Krystal Fontaine, a virologist who specializes in dengue at the Gladstone Institutes of San Francisco. “There was a surge in dengue infections in 2015 in Brazil, the same year Zika infections began skyrocketing.”
Clinicians and researchers also need a better diagnostic test for Zika. The most accurate method catches bits of the viral genome in a blood sample while a person is infected. But there’s only a one-week window before the virus clears from the infected person’s blood. Because of that and relatively mild symptoms, Zika infection in adults likely passes unnoticed.
After the infection is gone, other blood tests can find antibodies, but it’s unclear if those antibodies were generated against Zika or another Flavivirus—a condition called cross-reactivity. “For good epidemiological studies, it’s important to make it clear that you’re not measuring something else, especially in these [co-infection] areas,” says Melanie Ott, who runs the Gladstone lab where Fontaine works.
A more accurate, detailed count of infected people would also help answer other questions, says epidemiologist Justin Lesser of the Johns Hopkins Bloomberg School of Public Health, such as, “What is the risk of microcephaly per infected pregnancy? And, is something different happening with Zika in the Americas than elsewhere in the world, or is what we are seeing only the result of an especially large number of infections?”
Ott says other unknowns about Zika—for example, does it linger in saliva and semen longer than it does in blood?—make for more questions than answers when it comes to planning a vaccine. “I would think [a vaccine] would be geared toward young women and girls but what we know about Zika is just evolving. We don’t know whether it’s hiding somewhere in people, or if there’s recurrence if you’ve been infected by another strain, which is the dengue problem,” she says. “We don’t know what to expect.”
Among Ott’s first experiments with Zika, samples of which only arrived in her lab last month, will be ones centered on tiny lipid, or fat, droplets that are like storage … Next Page »