Zika Vaccine Works in Monkeys, Set for Human Trials
On the eve of the Olympics' opening ceremony in Rio de Janeiro, there's good news on combating the Zika virus: a promising vaccine effective in monkeys and now being fast-tracked for human clinical trials.
A purified, inactivated Zika virus vaccine earlier found to work in mice is effective against Brazilian and Puerto Rican strains of the virus in monkeys, too, researchers from the Walter Reed Army Institute of Research and Harvard Medical School reported in a study out on Thursday in the journal Science.
Phase 1 clinical testing of the vaccine, developed by the Walter Reed Institute, is expected to start in October.
The mosquito-borne Zika virus has been linked to the birth defect microcephaly and has spread throughout the Caribbean and Latin America, prompting some top athletes to pull out of the Olympics. It appears to have spread to the mainland United States, too; officials believe several cases in Florida were transmitted by mosquitoes there.
In the study, the researchers gave eight control-group monkeys sham vaccines and an additional eight the inactivated-virus vaccine. They also transferred antibodies from the vaccinated monkeys to mice and other monkeys.
Within two weeks, the vaccinated monkeys developed Zika-specific antibodies capable of fighting the disease. Animals given sufficient levels of those monkeys' antibodies, or titers, were also protected, the researchers found.
Perhaps most striking, immunity required "relatively modest" titers, said co-senior author Dr. Dan Barouch, a Harvard Medical School professor and director of Beth Israel Deaconess Medical Center's vaccine research center.
“These titers should be relatively achievable by these vaccine platforms in humans,” he said. “The fact that those antibody titers protect [against the virus] is really the reason why these data are powerful and provide this optimism for the development of clinical vaccines.”
Barouch and a Harvard team developed two other Zika vaccines that the study found effective in monkeys: a DNA vaccine and a recombinant adenovirus vector vaccine. But inactivated-virus vaccines, killed forms of the virus that usually require several doses or booster shots to offer immunity, have traditionally been used against mosquito-borne viruses such as dengue.
"They’ve been proven to be safe and effective and have been licensed by major regulatory agencies," said senior co-author Colonel Stephen Thomas, a vaccinologist who specializes in such viruses.
DNA vaccines, which use genetically engineered DNA to generate an appropriate immune response, can offer longer-lasting immunity and don't require booster shots. But they may not be as practical for Zika, said study author Colonel Nelson Michael, who co-leads the Walter Reed Institute's Zika program.
"Early on, [DNA] looks really sexy. But you have to ask yourself the downstream question," he said, adding that "we’re not here to protect mice, we’re here to protect humans.”
Compared with the DNA vaccine, far less of the inactivated-virus vaccine was needed for it to be effective, he said. A monkey had to be given 100 times as much (5 milligrams) of the DNA vaccine as a mouse received, but it needed just 5 micrograms of the inactivated-virus vaccine—five times as much as a mouse got.
“Giving more than 5 milligrams of DNA in a single shot is really hard. In order to make it a reasonable concentration to put into a human’s arm, it’s almost like syrup,” Michael said. “You really begin to exceed the ability of the technology to be feasible in terms of a public health tool.”
DNA and recombinant adenovirus-vector vaccines are the “vaccines of the future,” Barouch said. There are currently no clinically licensed DNA vaccines for human diseases, but the federal government and private companies have begun testing such vaccines on volunteers in recent weeks—testament to how fast companies can move to develop them.
A batch of the inactivated-virus vaccine has already been manufactured for clinical trials. Last month, the Army agreed to transfer its vaccine technology to Paris-based drugmaker Sanofi SA for further development.
It could take an additional three or four years before vaccines are mass-produced and make it to shelves, but Thomas said that such a period “really is light speed” in developing vaccines.
Just 2,000 doses or so are needed for testing, but 100 million are needed to address a crisis such as Zika in a country like Brazil, he said. The partnership with Sanofi—which has produced vaccines for dengue, yellow fever, and Japanese encephalitis—will be key to scaling up production.
“This is a really, really good marriage,” he said.
And given the public health crisis posed by the mosquito-borne Zika virus, researchers say it's urgent that they develop a vaccine that can be practically administered on a large scale.
“For a public health tool, especially in the middle of a crisis, it’s smart not to bid on a single horse,” Michael said.