A female Aedes aegypti mosquito, the species of mosquito primarily responsible for the spread of the Zika virus. (Image courtesy of the CDC)
As mosquitoes carrying the Zika virus spread illness to people across the Americas and beyond, scientists at Walter Reed Army Institute of Research are moving quickly, conducting preclinical research on a Zika vaccine candidate with collaborators at the Beth Israel Deaconess Medical Center and planning to start human testing before the year ends.
The process has gone quickly, Army Col. (Dr.) Stephen Thomas said during a recent DoD News interview, because the institute’s scientists know their flaviviruses. These include the mosquito-borne viruses that cause yellow fever, dengue, Japanese encephalitis and Zika virus diseases.
Thomas, an infectious disease physician and a vaccinologist specializing in flaviviruses, is the former deputy commander for operations at WRAIR in Silver Spring, Maryland, and the Zika program lead.
The Centers for Disease Control and Prevention is tracking active Zika virus transmission in 39 countries and territories in the Americas, eight in Oceania and the Pacific Islands, and one in the western African island nation of Cape Verde.
In the continental United States, CDC reports 618 travel-associated Zika cases, 11 sexually transmitted cases, one case of Zika-related Guillain-Barr syndrome, but so far there have been no reports of locally acquired mosquito-borne cases.
“Zika is a flavivirus, and we have been working on flaviviruses our entire history – since 1893 [on yellow fever],” he said. “So it’s in our DNA to work on flaviviruses, and we’ve been doing vaccine development for flaviviruses since World War II.” He noted that before Albert Sabin developed a polio vaccine, he was in the Army and helped to develop vaccines for dengue and Japanese encephalitis.
Because of that background and ongoing biosurveillance efforts, Thomas said, “when we started to see signals of increased Zika activity in southeast Asia a couple of years ago, it made sense that when we really started to see the uptick in activity in Central and, primarily, South America that we should bring our subject-matter expertise and our capabilities to bear as part of the whole-of-U.S.-government response.”
And then there was the clock.
“There’s a race to get this done as quickly as possible,” he said, “because there’s a public health emergency going on,” and because WRAIR is focused on supporting U.S. force readiness for service members deployed worldwide.
One of the reasons WRAIR can move fast on vaccines is its Pilot Bioproduction Facility for vaccines and biologics, established in 1958 to develop vaccines for Defense Department mission-related disease threats.
Today the facility also manufactures clinical-grade material for clients in the public and private sectors through cooperative research and development agreements, according to the WRAIR website.
“The vaccine facility belongs to us, so we’re able to control what they work on and when they work on it, and we’re able to be very agile and redirect resources when we need to,” Thomas said, adding that the facility produces 15 to 20 vaccine candidates a year.
Something else that helped WRAIR scientists get a head start on Zika vaccine prototypes is a biosurveillance program conducted at one of the three WRAIR overseas expeditionary research laboratories, this one in Bangkok.
Estimated range of Aedes aegypti and Aedes albopictus in the United States, 2016. (Image courtesy of the CDC)
The U.S. Army medical component of the Armed Forces Research Institute of the Medical Sciences was established after a cholera epidemic in 1956. The laboratory is an agency of the U.S. Embassy-Thailand and is located at the Royal Thai Army Medical Center in Bangkok.
Together, AFRIMS in Southeast Asia and U.S. Army research platforms in Tbilisi, Georgia, and in Kenya, Mozambique, Uganda, Nigeria and Tanzania constitute special WRAIR foreign activities and form one of the largest pieces of a global DoD network. The network includes Navy medical research labs in Peru, Singapore and Egypt, a detachment in Ghana, and partner labs around the world.
“At the end of last year, we started to talk amongst ourselves that this Zika signal was starting to heat up,” Thomas recalled. “We had seen what happened with [mosquito-borne] dengue in Central and South America [beginning] in the ’80s. … It went from having very little activity, and when the … viruses got introduced through travel and other means, it really took off.”
Thomas and his colleagues also watched chikungunya — a mosquito-borne alphavirus that likely originated in central and east Africa – make its way to Central and South America and the Caribbean between 2007 and 2013.
“It was the same scenario playing out again and again, where you have this susceptible population because the virus has not circulated there before, so they have no herd immunity,” Thomas said. “Then you have the vector, in this case mosquitoes, capable of transmitting, and then you get introduction of the virus into that area and it starts taking off. We saw it with dengue, saw it again with chikungunya and … we saw it in this country with West Nile.”
Because of Zika virus biosurveillance at AFRIMS in Bangkok, Thomas and his colleagues were able early on to get a strain of Zika from Asia that allowed them to do initial experimentation while they waited to get another strain that would be a basis for the vaccine, he said.
Zika Vaccine Effort
Thomas and his colleagues considered many factors when planning the Zika virus vaccine development effort, he said, including a charge by DoD to get something in the field as quickly as possible while mitigating regulatory agency risk and speeding up the process where possible, he said.
He explained regulatory risk this way: “We are working on a type of vaccine that the [Food and Drug Administration] has seen before and has licensed before,” Thomas said. “It’s the same [cell-based] technology we used to develop the Japanese encephalitis vaccine.” The researchers are trying to mitigate risk by avoiding unproven technologies that could cause a licensing delay, he noted.
WRAIR is working on the vaccine in collaboration with other U.S. government agencies, including the Biomedical Advanced Research and Development Authority — part of the Department of Health and Human Services — and the National Institutes of Health National Institute of Allergy and Infectious Diseases. It is also exploring collaborations with pharmaceutical companies, Thomas said.
The vaccine will contain a killed strain of the virus that is circulating now in South America, he added.
“This is not something like dengue, where there are four dengue virus types and you have to include every type,” he explained. “We feel pretty comfortable that for an initial vaccine construct, a single strain will be sufficient. We believe that it’s a good idea [to use] the strain that is causing the congenital syndromes and neurologic defects appearing in that region.”
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