DGHI Professor and Penn Colleagues Develop Zika Candidate Vaccine

About a year ago, when Zika began to emerge as a potential epidemic, Barton Haynes, director of the Duke Human Vaccine Institute (DHVI), told the researchers in the DHVI’s Regional Biocontainment Laboratory, “Let’s get the Zika isolates, set up a Zika neutralization assay, learn to grow the virus and get ready to face this epidemic.”

It was this early preparation that laid the groundwork for the rapid development and initial testing of a Zika candidate vaccine. This research, conducted in collaboration with Drew Weissman and other University of Pennsylvania researchers, was recently published in Nature.

The vaccine is based on genetic immunization with a chemically stabilized messenger RNA (mRNA) that encodes the pre-membrane and envelope glycoproteins of the Zika virus. A single dose of the vaccine gave mice and rhesus macaques long-term immunity to the virus.

Weissman and co-first authors Norbert Pardi and Michael Hogan developed the candidate vaccine, and the study was conducted at the DHVI. The first immunization took place in August, and the paper was published in February—an extraordinarily short time period to produce such promising results.

Haynes, the Frederic M. Hanes professor of medicine and immunology and global health, says that the key to the success of the vaccine was twofold. 

First, when RNA is injected into an animal or human, the immune system typically recognizes it and fights against it. But Weissman figured out how to cloak the RNA so that the immune system wouldn’t attack it, enabling the RNA to produce as much protein as possible. And secondly, the vaccine was injected intradermally, allowing it to reach the right cells to maximally stimulate the immune system. 

Vaccination with mRNA offers several advantages over other vaccine platforms: 

• It avoids the safety risks and anti-vector immunity associated with some live virus vaccines
• It’s a non-integrating, non-infectious gene vector that can be designed to efficiently express any protein 
• It has the potential for cost-effective and highly scalable manufacturing
• Small doses can induce protective immune responses

Haynes was astonished by the findings. “We were initially conducting the study as a control for our HIV vaccine work,” he said. “We gave the animals one shot [of the vaccine], and they produced such an intense immune response that we went ahead and challenged them with the Zika virus—and they were 100 percent protected.” 

Haynes believes genetic immunization with mRNA may be the wave of the future for vaccines. The DHVI is currently working on an HIV vaccine that incorporates mRNA.

As for the Zika candidate vaccine, Weissman and his colleagues are exploring intellectual property issues and seeking companies to produce the vaccine for human clinical trials.

This study was funded through grants from the National Institutes of Health (NIH).

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