Tuesday, 23 August 2016 12:00

Onward toward a Zika vaccine

Written by 
Published in mBiosphere

By: Stephen Ornes

On Monday, August 1, the US Centers for Disease Control and Prevention recommended that pregnant women not travel to Wynwood, a neighborhood north of downtown Miami, because health officials in Florida had found that mosquitoes there are actively transmitting Zika, a mosquito-borne virus that can cause birth defects. (It can also be spread through sexual contact.) The recommendation also included guidance on mosquito avoidance for pregnant women who live in the area, as well as people planning to conceive a baby.

This recommendation marked the first time the CDC has issued a travel warning for a locale within the United States. Babies born to mothers infected with the virus have been reported to have microcephaly – a condition where a baby's head is much smaller than expected, given the size of the body – and other potentially fatal defects. (In April, the CDC announced it had analyzed enough evidence to clearly know that the virus causes the defects.)

Zika was first identified in Uganta in 1947, but for decades it remained quiet, rarely spreading beyond a narrow geographical area around the equator in Africa and Asia. The current Zika pandemic began last year in Brazil and quickly exploded; it has spread to more than 30 countries in the Americas. About 80 percent of infected people are asymptomatic, which means it's difficult for people to know their own risk. Babies with birth defects have been born to mothers who didn't know they hosted infections. Scientists don't yet know the long-term consequences for children born to infected mothers who don't show signs of microcephaly.

The unknowns about Zika and its consequences have spurred biologists and other researchers to search for new genetic strategies and models that might guide the development of a vaccine. One of the most important tools for this purpose is a virus clone that can be used to guide and test treatments and vaccines. In May, researchers from the University of Texas Medical Branch, in Galveston, published a report on the first Zika clone derived from viral complementary DNA, or cDNA.

That work was based on a strain isolated from a patient in 2010, during a Zika outbreak in southeast Asia. In a new study published this week in mBio, molecular biologists led by Alexander Pletnev at the NIH's National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, point out that the strain used in that the clone differs from the viral strains behind the current pandemic.

Pletnev and his collaborators generated a cDNA clone based on an epidemic strain isolated from a febrile patient in Brazil in 2015. The clone is closely related to strains behind the current pandemic that cause human fetus microcephaly. The cloned virus remained stable and infectious in multiple lines, including placental and brain cells. High-throughput genetic sequencing showed that the clone was similar – but less genetically diverse – to the wild-type parent.

The researches genetically modified their ZIKV clone to grow in cells used for human vaccine production, and they believe that their attenuated clone is a convenient platform for designing new vaccines and therapies, and Pletnev says he encourages other researchers in the field to use it to accelerate research on Zika. Based on the success of these lab studies, Pletnev's team has now begun experiments on animal models, with the ultimate goal of producing a vaccine that delivers long-term immunity after a single inoculation.

Pletnev's group only began working on Zika in the spring of 2016. They're also actively working on vaccines for other Flaviviruses – the genus that includes Zika – including West Nile and dengue. Pletnev's group is also developing a vaccine for the chikungunya virus, and he thinks work on that virus will inform research on Zika.

“These two viruses share same geographic area and are transmitted in same mosquitoes, so it seems reasonable to create immunity against both viruses,” he says.