Virus

DNA may offer rapid road to Zika vaccine

Zika DNA vaccine
A Zika vaccine that’s made of DNA could be a safe and fast way to protect people from the virus, which can cause birth defects.

GIVE IT A SHOT

Last August, scientists injected a potential vaccine for Zika virus into a human being — just 3½ months after they had decided exactly what molecular recipe to use.

In the world of vaccine development, 3½ months from design to injection is “warp speed,” says vaccine researcher Nelson Michael of the Walter Reed Army Institute of Research in Silver Spring, Md. Clinical trials can take years and epidemics can burn out before vaccines make it to doctors’ shelves. Even vaccine creation is typically sluggish.

But in this case, the vaccine is a bit of DNA, which means scientists can get moving fast. Unlike some traditional methods, DNA vaccines don’t use dead or weakened viruses. Instead, they rely on a snippet of genetic material. This “naked” DNA carries, for example, the blueprints for Zika proteins. It’s just a long sequence of DNA blocks.

With DNA vaccines, “it’s easy to move very quickly,” says Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Md. “All you need to do is get the right sequence, and Bingo! — you’re there.”

Historically, though, DNA vaccines have been deviled with drawbacks. “They work absolutely fantastically in mice,” says infectious diseases physician Anna Durbin of Johns Hopkins Bloomberg School of Public Health. But “they fail miserably when we use them in humans.”

Researchers at the infectious diseases institute will soon begin the second phase of human clinical trials for a DNA vaccine candidate for Zika, vaccine clinical researcher Julie Ledgerwood said February 6 in Washington, D.C., at an American Society for Microbiology meeting on biothreats. The virus made headlines last year as it continued its tear through the Americas, and scientists confirmed its link to birth defects, including microcephaly (SN: 12/24/16, p. 19). Ledgerwood hopes to see efficacy data on the vaccine by the end of 2018.

“Ultimately, we want a vaccine that can prevent congenital Zika infection,” she said. “We think the DNA vaccine platform is an opportunity to do things safely and very quickly.”

Government researchers aren’t betting everything on DNA, though, Fauci points out. “We’ve got multiple shots on goal here,” he says. A slew of other vaccine candidates, based on both traditional and new techniques, are also in the works. But the DNA vaccine has stepped up to the plate first, and the world will soon see if it can deliver.

“If it works,” Durbin says, “we’ve hit a home run.”

Making a DNA vaccine is simple, in principle. Scientists synthesize genes from a pathogen, insert them into a circular strand of DNA called a plasmid, make lots of copies and then inject the purified plasmid into a person. “You can literally build a DNA vaccine in weeks,” says Dan Barouch, an immunologist at Beth Israel Deaconess Medical Center and Harvard Medical School. The approach is flexible, too, he adds. Researchers can tinker with the DNA building blocks in the plasmid, adding bits from other viruses that might ultimately enhance the immune response.

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Immune trigger

For a DNA vaccine against Zika, scientists insert genes for Zika proteins into a circular piece of DNA called a plasmid. Many copies of the plasmid are injected into muscle. Some of the DNA travels into cells’ nuclei, where it is used to make messenger RNA. After exiting the nucleus, mRNA helps build Zika proteins, which can form viruslike particles that trigger the immune system to make antibodies.

Zika DNA vaccine process

Barouch’s team was the first to report a Zika DNA vaccine that offered protection in mice — in a study published last June in Nature. Five weeks later, he and colleagues reported in Science that the vaccine, and two others created via different strategies, worked well in monkeys, too. And in September, a team led by government scientists, and including Barouch as a coauthor, came out with two additional DNA vaccine candidates, described in Science.

It’s one of those additional candidates, called VRC 5283, that the infectious diseases institute plans to test in…