A plant typically thought of as a disease instigator may hold the key to hindering future influenza illness.

University of Nebraska–Lincoln virologist Eric Weaver is leading a new project interrogating the tobacco mosaic virus as a possible catalyst for developing a universal flu vaccine — as both a way to replicate the viral antigens quickly and deliver them in vaccine form.

“There is an absolute beauty in the fact that we may use something that took America a long time to realize just how dangerous it was to consume, and turn it around to use it as a tool to promote health,” said Weaver, associate professor in the School of Biological Sciences and the Nebraska Center for Virology.

The five-year, $3.2 million grant from the National Institutes of Health’s National Institute of Allergy and Infectious Diseases combines the expertise of Weaver and scientists from St. Jude Children’s Hospital, Touro University California and Kentucky BioProcessing.

“This grant is founded on the use of using the tobacco mosaic virus to deliver the vaccine immunogens, as well as producing those immunogens in tobacco plants,” Weaver said. “The tobacco mosaic virus was one of the first viruses isolated and studied — it’s probably one of the most studied viruses in all of biology. It infects tobacco plants, and it’s relatively benign to people.

“We’re taking a virus that has been studied for over 100 years, and we’re decorating that virus with antigens or the immune agents for the vaccine.”

The team will attach influenza hemagglutinin — the spike protein that extends from the surface of the virus and attacks cells causing illness — and a similar protein referred to as M2 to the tobacco mosaic virus to produce antigens and grow them in the tobacco plants. Weaver said the team will be working with hemagglutinin from three subtypes of influenza virus: H1, H3 and H5.

“This makes it more complicated, as we’ll be using many different components in the vaccine to make it as broadly effective as possible,” he said.

The new grant builds on decades of Weaver’s research, which focuses on tracing flu viruses’ genetic pasts to find the proteins that could be used to design a universal flu vaccine. Through selecting and stringing together the ancestral viral components, Weaver’s research has shown that the method does induce protection against divergent flu viruses — no matter how much they mutate.

“Those same foundational or ancestral genes, those hemagglutinins are a proponent of this proposed vaccine model,” he said.

It also builds on technologies developed during recent disease outbreaks. While examining ways to treat Ebola in 2015, scientists conducted experiments to produce antigens in plant viruses, including the tobacco mosaic virus. Kentucky BioProcessing was successful in developing ZMapp, an experimental drug credited with saving two Americans who contracted the disease. At the time, the company also was able to show that using the method could possibly scale up vaccine production quickly — as much as 5 million doses in 30 days.

“The thinking at the time was ‘let’s put some things in place for rapid vaccine production,’” Weaver said. “If we can take these vaccine immunogens and produce them in plants at high production levels, under clinical manufacturing protocols, we can rapidly go from a novel pandemic pathogen to a vaccine in a very short period of time. We can deliver a vaccine in a variety of ways — we’ve used attenuated viruses, viral particles, animal models — and the proposal here is to use a plant virus.

“The beauty of the conjugated tobacco mosaic virus platform is that once they’re created, they’re self-replicating viral particles. The speed and the scalability of this platform is the biggest advantage.”

Once the vaccine and delivery model are developed, Weaver said the grant also covers small animal model trials. The ultimate goal is to have a universal flu vaccine combining antibody and cellular immunity that is long-lasting.

“This is a five-year grant where we’ll do testing in pre-clinical animal models,” Weaver said. “We have a plan and if all goes well, hopefully funding would be extended and we move into human clinical trials. It’s following a typical vaccine timeline of between five and 15 years.”

Nebraska Center for Virology Virology