Just five months after the Zika virus was declared a global public health emergency, a scientific team’s feverish efforts to create a vaccine against the viral threat have borne promising fruit: With a single shot of either of two different types of vaccine, experimental mice gained near-total immunity to Zika for at least two months.
Writing in the journal Nature on Tuesday, a U.S.-Brazilian team of scientists reported that two distinct vaccine candidates conferred powerful protection from Zika infection when each was delivered by intra-muscular injection to mice.
“We were very surprised — and quite impressed — that a single shot of either of these vaccines provided complete protection,” said study co-author Dr. Dan H. Barouch, who after years of work on vaccines against HIV pivoted in late January to work on Zika.
“Of course, we need to be cautious about extrapolating” from a study that has so far only shown success in mice, said Barouch, who directs vaccine research at Beth Israel Deaconess Medical Center in Boston.
But several of the study’s findings “certainly raise optimism that the development of a safe and effective vaccine against Zika virus for humans may be successful,” he added.
The Zika vaccine effort is a race against time. Since its arrival in Brazil in 2013, the Zika virus has marched steadily north. Carried by the Aedes aegypti mosquito, the virus is already spreading vigorously in Puerto Rico and is expected to circulate inside the continental United States this summer.
The Centers for Disease Control and Prevention has concluded that Zika infection in pregnant women can cause grievous brain abnormalities in the infants they bear. For those who are not pregnant, Zika infection is generally not dangerous. But in rare cases, it can cause Guillain-Barre syndrome, a life-threatening condition in which the immune system attacks the peripheral nervous system, causing partial paralysis that is generally temporary.
The Boston-based team also discerned how the tested vaccines worked to provide protection — an important milestone in building a vaccine. Soon after their first shot of either vaccine, the immune systems of lab mice quickly mobilized an army of circulating antibodies that recognized and attacked Zika virus as soon as it began replicating.
Such “antibody protection,” produced by the immune system’s B-cells, is not generally as enduring as the long-term immune memory produced by T-cells. But “it’s good: it makes a vaccine that’s nice and neat and simple,” said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.
Fauci called the vaccine candidates’ early success “an important step on the road to getting vaccines into humans.” He confirmed that several other Zika vaccine candidates are being tested in animals, and that very early testing in humans could begin as early as late August.
The two vaccine candidates described in Nature represent two very different approaches to training the immune system’s killing power on the Zika virus. One takes the whole of a single Zika virus, inactivates it by removing the machinery that makes it replicate, and shows it to the immune system.
The other candidate, a so-called DNA vaccine, shows the immune system only the distinctive outer sheath of the Zika virus in a bid to prompt attacks on anything enclosed in such an envelope.
Both approaches worked in several different strains of laboratory mice. But while “inactivated virus” vaccines are already in wide use, DNA vaccines, have never been approved for use in humans in the United States.
“Some call them vaccines of the future,” said Barouch of the DNA vaccines. Whether they lend themselves to large-scale production and distribution remains unclear, he said. “But they do have a variety of … technological advantages compared to the traditional approaches” — not least that vaccine designers can make rapid changes in the mix of puzzle pieces shown to the immune system.
Given the uncertainties of developing vaccines for emergency use, “a diversity of approaches is always beneficial,” he added.
Indeed, at least one other vaccine candidate — a DNA vaccine designed by the drugmaker Inovio Pharmaceuticals Inc. of Pennsylvania — is also moving toward clinical trials in humans. Last week, Inovio said it had received the go-ahead from the U.S. Food and Drug Administration to test a synthetic vaccine called GLS-5700 that it said “induced robust antibody and T-cell responses in small and large animal models.”
The company has not published the results of its tests, but it expects to begin a clinical trial with 40 healthy subjects “within weeks,” said company spokesman Bernie Hertel.
In the experiments reported in Nature, the mice cleared Zika virus from their bloodstreams even when their army of antibodies was “relatively modest,” Barouch said. With an additional booster shot or two, he said the experimental vaccines could prompt an immune response a hundred times as strong, if needed.
One other factor should prompt optimism that this early success might lead to a timely vaccine, said Barouch: Immunologists have had success in building vaccines against viruses in the same family as Zika, including those that cause yellow fever, dengue fever and Japanese encephalitis.
In a related development reported Tuesday in the journal Nature Communications, scientists concluded that macaque monkeys, which have become a mainstay of nonhuman primate research with the diminishing use of chimpanzees, respond to Zika virus infection in ways that strongly mimic humans’ reactions.
That finding means scientists will have a highly reliable stand-in for testing the safety and effectiveness of vaccines and other new therapies against Zika before they are administered to humans. The ability to use macaques to approximate a human’s response to the two vaccine candidates already tested, as well as to test other vaccines under development, will be key to speeding the development of such medications.
Still, many hurdles remain.
Among the challenges for a Zika vaccine, says Mayo Clinic immunologist Dr. Gregory Poland, is that it will likely be used to protect diverse populations with very different risks, and must be found acceptably safe in all.
A vaccine that is safe for younger women — who could be pregnant or become pregnant — may not be the same as a vaccine that protects older patients, who are at greatest risk of developing Guillain-Barre syndrome following infection, said Poland. As testing proceeds, he added, researchers and regulators will also have to find a vaccine safe for use in populations that span the spectrum of age, gender, ethnicity and medical history.
“Under the normal course of events, it could take years,” said Poland. “There’s just a whole lot of complexity here.”
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3:42 p.m.: This article was updated with additional information about Inovio Pharmaceuticals’ plans for a clinic trial.
2:53 p.m.: This article was updated with Inovio Pharmaceuticals’ announcement that it had received FDA approval to begin tests of a synthetic Zika vaccine, GLS-5700.
This article was originally published at 11:06 a.m.
An earlier version of this article incorrectly said Inovio Pharmaceuticals Inc. was based in South Korea. It is in Pennsylvania.