Husband-Wife Team Pioneers Zika Vaccine to Last a Lifetime

A husband-wife team of biochemists at NC State is testing a one-shot vaccine that could grant lifetime immunity against the widely feared Zika virus.

Drs. Dennis Brown and Raquel Hernandez of the Department of Molecular and Structural Biochemistry have developed a method to limit the protein-level association of amino acids that hold the virus’ particles together. This weakens the virus in humans, triggering a potent immune response. The immunity is long term and will protect the person from subsequent infection.

The vaccines are still in clinical trials, Brown cautioned – but based on results with related viruses like dengue fever, the couple is optimistic.

“We believe our vaccines will give lifetime immunity,” said Brown, a William Neal Reynolds Distinguished Professor. “We have the only platform that can guarantee complete protection.”

“Priority One”

Zika is a mosquito-borne flavivirus with symptoms ranging from mild fever to serious birth defects, according to the World Health Organization. An outbreak in the Americas in 2015 caused a worldwide scramble to figure out how to combat or prevent the disease.

Brown and Hernandez started work on zika when the health crisis crested earlier this year.

“It’s been priority one,” Brown said. “Everything else has gone on the back burner.”

Their work is based on an earlier discovery by Hernandez: the bond between proteins needed for an “assembly event” – replication and spread of the virus to a healthy cell – could only happen if their amino acids lined up just right. By deleting key sections of the protein, Hernandez discovered she could make it too short for the necessary amino acids to connect, preventing the virus from infecting healthy cells. This was possible, the couple discovered, because insect cell membranes are much thinner than those in mammals.

“We have a historically-proven approach to the development of this vaccine, which is a live attenuated vaccine,” said Hernandez, a research associate professor of biochemistry.

Of the 700 currently known mosquito-borne illnesses, 150 cause illness in humans – and using this platform based on their decades of work, Brown and Hernandez can now create live, attenuated vaccines against any of them within months.

The work requires caution. For their Zika experiments, the research team works in a level three biocontainment laboratory. Protective clothing is required.

What’s Next?

Currently, the couple has three candidates for a publicly available vaccine being tested in pre-clinical trials. Each vaccine is different by just a few amino acids. They will evaluate which one grows best, is most stable and produces the best immune response for further testing. Each step requires meticulous care and thorough testing.

Other vaccines currently in development will require periodic re-vaccination, Brown said. Theirs is designed to be a “one and done” vaccine.

It took decades of work on related viruses to get to this point. These innovative leaps in understanding were sparked by one of the most basic motivators: curiosity.

“Originally, we just wanted to understand how viruses are put together and how they work,” Brown said. “This is something that came serendipitously.”