Penn researchers made an avian flu vaccine using a technique that created COVID vaccines

University of Pennsylvania researchers have developed an mRNA vaccine for the H5N1 avian flu drawing increasing scrutiny by public health officials. The vaccine is effective against the virus in mice and ferrets, according to a new study published Thursday.

The Penn team is using the same technique that powered the speedy development of a COVID-19 vaccine when a novel virus turned into a global pandemic.

The highly virulent strain of avian flu currently poses little risk to people. But it has infected millions of birds around the country in the last several years, including flocks in Pennsylvania. In March, the virus began turning up in herds of dairy cattle, eventually spreading to nine states. (Pennsylvania and New Jersey have not seen avian flu outbreaks in cattle; the closest reported cases are in Ohio.)

H5N1 so far is not highly contagious among humans. Still, its jump between domestic animals is a concern for public health officials, who fear the virus could mutate to more easily infect humans. The second case of H5N1 in a person in the United States was reported Wednesday by federal authorities. The two known cases involve a pair of agricultural workers in Texas and in Michigan.

The potential for further spread in people underscores why it’s important for researchers to develop new vaccines and test their safety before the virus could make that leap, said Scott Hensley, a Penn professor of microbiology and the study’s corresponding author.

“It’s important to do a lot of these early clinical studies with viruses that pose a pandemic risk now, instead of in a pandemic,” he said.

The Penn research team that developed the vaccine includes Drew Weissman, who with his colleague Katalin Karikó won the Nobel Prize in Medicine in 2023 for their development of the technique that modifies messenger RNA, or mRNA, to instruct cells to build immunity against viruses.

The same technique that led to the Pfizer and Moderna COVID-19 vaccines was used to create the new H5N1 vaccine featured in Thursday’s study in Nature Communications.

Like with the COVID vaccines, the Penn researchers used mRNA to instruct the immune system to build antibodies against a specific protein in the H5N1 virus that allows it to attach to cells and replicate within the body.

“The antibodies stick to the outside of the virus, so it can no longer get into cells,” Hensley said.

Without mRNA technology, a more conventional flu vaccine would get produced by injecting the virus into a fertilized chicken egg, allowing the virus to replicate, and then deactivating it for use in a vaccine.

The benefit of mRNA vaccines, though, is that they can be produced and modified very quickly — crucial in a rapidly changing pandemic environment.

“If it [H5N1] were to jump into humans and cause a human pandemic, it would be very easy to modify that vaccine that we have now,” he said. “There are so many advantages of this tech — the ability to quickly update and scale up, and not having a dependence on fertilized chicken eggs, which is a tricky process.”

The researchers’ new H5N1 vaccine produced a high antibody response in mice and ferrets, Hensley said, adding that researchers tested the vaccine on mice who had never been exposed to the flu and mice who had been exposed to seasonal flu viruses to better replicate how the vaccine would perform in humans.

The researchers also saw high antibody responses in another group of mice inoculated with an H5N1 vaccine produced in a more conventional manner.

The group expects to begin tests on cattle, pigs, and chickens within weeks.

Penn researchers are not the only group working on developing H5N1 vaccines. Moderna is currently testing an H5N1 mRNA vaccine, and federal officials have said they have limited stockpiles of conventional H5N1 vaccine candidates as well.

Hensley said he’s concerned about the H5N1 virus’s potential to mutate: “Scientists get nervous because we’ve seen it happen historically where these viruses change — with one or two viral mutations, that can change the whole equation on pandemic risk,” he said.

But the current strain of H5N1 appears to pose little risk to the public, health officials say.

“Everyone doesn’t need to run to the pharmacy and stock up on toilet paper right now,” Hensley said.

The researchers’ initial goal was to produce a vaccine that was effective in humans, but Hensley said the group also sees potential for their new vaccine in inoculating livestock. If H5N1′s spread can be halted or slowed in livestock, the virus will have less of an opportunity to mutate and potentially affect humans.

“It’s important to protect livestock to reduce the amount of virus replicating in animals — which would also reduce the risk to humans,” he said.