Cornell researchers have developed a new vaccine platform that could provide more robust, longer-lasting protection from both COVID-19 and influenza, and broader immunity to different flu strains.
In a study published Jan. 29 in Science Advances, researchers found no visible signs of illness in mouse models after vaccination with the new platform and no cellular damage to tissues.
"One of the big moments was when we started achieving 100% survival and lack of clinical disease in all of the vaccinated mice following challenge with either SARS-CoV-2 or influenza virus," said Richard Adeleke, first author and doctoral candidate in the field of immunology and infectious diseases. "Then when there was no detectable virus in the tissues - we examined the lung and brain tissue post-infection - that was a moment of very big excitement. We were convinced. We thought, 'This thing is really working.'"
While current vaccines for SARS-CoV-2, the virus responsible for COVID-19, and influenza are both safe and variably effective, there remains room for improvement. COVID-19 mRNA vaccines are highly sensitive to cold temperatures, posing challenges for distribution and administration in regions without reliable cold-chain infrastructure. Meanwhile, current influenza vaccines, with efficacy often below 50%, struggle to protect against the numerous strains of the virus. Both vaccines also offer relatively short-lived immunity, requiring annual - or even more frequent - booster doses, making it harder to administer.
The new vaccine addresses these shortcomings.
"This is an exciting new modular technology that can accommodate glycoprotein antigens from many different viruses in a thermostable vaccine, making it possible to have dual, triple or more viral targets in the same vaccine," said senior author Hector Aguilar-Carreno, professor of virology in the College of Veterinary Medicine (CVM) and associate vice provost for research & innovation in the Office of the Vice President for Research and Innovation. "Having multiple viral targets in the same vaccine makes the vaccine manufacturing process easier and cheaper."
In addition to prompting complete immunity, researchers found that the neutralizing antibodies persisted in the mouse models eight months after vaccination. When a different influenza strain was introduced, the vaccine protected against that strain as well - a breakthrough that could vastly improve the standard flu vaccine's efficacy.
"Even achieving efficacy consistently above 50% is a huge step," said David Buchholz, Ph.D. '22, corresponding author and postdoctoral researcher. "When we found protection with this vaccine from a different strain - it may not sound like much, but that's really the start of the holy grail pursuit when it comes to influenza vaccines."
To develop the vaccine, researchers used vesicular stomatitis virus (VSV), a virus that infects mainly horse and cattle, but altered it to remove glycoproteins from the virus particle's surface - a step that makes the virus incapable of replicating or becoming virulent. Then the researchers added to the surface the spike protein found on the surface of SARS-CoV-2 and a neuraminidase protein found on influenza A. The vaccine works by triggering the host immune system to produce antibodies in response to the two proteins.
The vaccine platform is thermostable, potentially making administration easier and more accessible than the current mRNA COVID-19 vaccines. For influenza, the neuraminidase protein is conserved across many strains of flu, prompting the immune response to multiple strains.
"The protein hemagglutinin is used to standardize flu vaccines because it is much more abundant on the surface of the virus," Buchholz said. "But it is less conserved across strains and more prone to mutation, so every year, there is a need to reformulate flu vaccines to match circulating strains."
Seven million people have died from COVID-19 since 2019, and the World Health Organization estimates that between 290,000 and 650,000 people die each year from influenza, many of them children younger than 5 in developing nations.
In addition to being more stable, the new vaccine might not be needed every year, which could increase vaccine participation, reduce the burden on health systems, make vaccination less expensive and more accessible and ultimately save lives.
"People might only need the vaccine every five years, or depending on how the next trials go, maybe it will provide lifelong immune protection," Adeleke said. "We're now trying to push this in the public health direction - it takes a lot of time and money, but we're pursuing that as hard as we can."
Members of the lab have formed a startup, VIVA Viral Vaccines, Inc., to pursue development and clinical trials of the vaccine platform, which can be used to combat multiple viruses. In previous work, the team found that the altered VSV particle, with different proteins added to the surface, was effective against three of the most deadly viruses, Nipah, Hendra and Ebola.
"It's a modular platform," Buchholz said. "We can take whatever proteins we want, put those various combinations onto the surface. And multiple times, we've been able to get very good protection."
Co-authors include Gary R. Whittaker, the James Law Professor of Virology (CVM); Mason C. Jager, Ph.D. '22, assistant professor of population medicine and diagnostic sciences (CVM); Avery August, professor of immunology (CVM) and deputy provost; research associate Julie Sahler; postdoctoral researchers Annette Choi, Ph.D. '24, and Shahrzad Ezzatpour, Ph.D. '24, Brian Imbiakha, Ph.D. '24; former undergraduate researcher Kyle Roth '24; and doctoral students Viraj Upadhye, Solomiia Khomandiak and Annika Diaz.
The research was supported with funding from the National Institutes of Health, a Cornell Seed Grant for SARS-CoV-2 vaccine development, the Cornell University Ignite Program and the 3M Company.
