Diffusing a Global Threat with Nasal Spray

A Universal Vaccine for Respiratory Viruses Could Prevent the Next Pandemic

In 2015, five years before the COVID-19 pandemic swept around the planet, Bill Gates opened a TED talk standing before an image of a nuclear explosion saying: “Today, the greatest risk of global catastrophe doesn’t look like this.” The screen changed, and Gates pointed to an image of the virus that caused the 2009 swine flu pandemic and said, “Instead, it looks like this.”

The spikey ball was an unfamiliar image back then, but today, it is widely understood that such viruses pose a global threat to human health and economics.

Gates’ announcement was not prophetic. It was a logical statement based on science that remains true today. Despite the huge advances in medicine since the start of the COVID-19 pandemic, the world is still not prepared to stop the next new viral threat in its tracks, and COVID, along with the multitude of variants that may arise, remains a hazard today.

But what if there was a universal vaccine for all variants of COVID that was safe, effective and easy to administer as a nasal spray? And what if it could be rapidly adapted to confer immunity to any respiratory virus, whether COVID, the annual flu, or some new disease that has yet to emerge?

Xiaoping Zhu has been developing just such a vaccine, and his patented new technology is ready to be tested in humans. In 2019, Zhu, a professor and chair of UMD’s Department of Veterinary Medicine, received $3.1 million from the National Institutes of Health to develop a universal nasal vaccine for the flu, but in January 2020, he redirected his efforts toward COVID-19.

What makes Zhu’s approach particularly innovative is his use of a protein to deliver the desired vaccine into the body. Other nasal vaccines use a piece of a virus or a live, inactivated virus. Zhu’s protein-based system can be engineered to deliver an antigen for the COVID-19 spike protein or other antigens like those for the seasonal flu. His unique technology won the 2022 UMD Research Invention of the Year Award.

“Our protein-based vaccines target proteins among all strains of a virus, so the variant doesn’t matter,” Zhu said, “And it is safer for higher-risk populations that are more susceptible to infection, like the very young, the elderly, and immunocompromised.”

Zhu specifically focused on developing a nasal spray, because it has many benefits over injection-based vaccines, especially for respiratory diseases. In animal trials, Zhu’s nasal vaccine produced a strong immune re­sponse in the airway, and those are the cells that become infected first with COVID and other respiratory diseases. His vaccine stops the infection at the door, before it has a chance to get into the lungs and bloodstream.

“Vaccination in the arm induces good levels of antibody in the blood, but there is less antibody in the nose—the site where the infection actually starts, where the virus begins to replicate,” said Jeffrey Cohen, chief of the Laboratory of Infectious Diseases and Medical Virology Section of the National Institute of Allergy and Infectious Diseases, who is not involved in Zhu’s research. A nasal vaccine “would not require an injection and it would be delivered to the site of COVID infection…A strong immune response in the nose and upper airway might also reduce shedding if infection occurs and reduce spread to other persons.”

As Zhu prepares to take his vaccine to human trials, he is already working on the second generation technology, which targets the tiny piece of the spike protein that docks with part of a host’s cell. This docking bit allows the virus to wheedle its way inside a cell. Zhu’s next generation vaccine would prevent the virus from docking, shutting down any chance of infection.

That would make a single vaccine effective against all variants of a disease, because the docking mecha­nism doesn’t change between variants. Zhu is using the same platform to develop vaccines that would protect against all new corona viruses as well as the seasonal flu.

Stability and ease of delivery means Zhu’s nasal spray vaccine could help shut down the COVID-19 pandemic in parts of the world where millions of people remain unvaccinated, and it would provide relatively easy boost­ers in countries with high vaccination rates, like the U.S.

No one knows when another new virus will emerge with pandemic potential, but with a room-temperature-stable, easily delivered, universal vaccine technology at the ready, Zhu and his colleagues just might be able to diffuse the threat, and prevent the next global catastrophe. Vaccines are easily produced and stable at room temperature, so they need no special storage,” Zhu said. “They could even be delivered to remote villages through the mail.

by Kimbra Cutlip : 
Momentum Summer 2022