Study: Three-in-one vaccine shows promise against ‘tripledemic’

BUFFALO, N.Y. — Flu season is no longer just flu season. Since 2022, the health care community has faced what’s known as a “tripledemic” of seasonal influenza, COVID-19 and respiratory syncytial virus (RSV).

That may mean that the flu shot needs to become more than a flu shot.

A single-shot vaccine under development at the University at Buffalo could protect against flu, COVID-19 and RSV simultaneously. In a study published today (June 26) in Science Advances, the researchers found that their three-in-one vaccine triggered protective immunity against all three respiratory diseases in mice, ferrets and cotton rats.

“The antibody responses were comparable to those produced by vaccines that target just a single virus, suggesting that combining the three vaccines into one shot did not weaken their effectiveness,” says corresponding author Jonathan Lovell, PhD, SUNY Empire Innovation Professor in the Department of Biomedical Engineering, a joint program of UB’s School of Engineering and Applied Sciences and Jacobs School of Medicine and Biomedical Sciences.

The work was supported by the National Institutes of Health and a McGill University Grant. 

The tripledemic was associated with approximately 1 million combined hospitalizations in the United States during the 2023–2024 respiratory virus season alone.

Despite the risks, only 35% of Americans aged 75 and older had received an influenza vaccine as of November 2024. About 18% had received a COVID-19 vaccine, while 40% had received an RSV vaccine.

“We know that many people skip one or more of the three recommended respiratory vaccines, sometimes simply because it’s inconvenient,” says co-author Bruce Davidson, PhD, research associate professor in the UB Department of Anesthesiology. “Replacing them with one annual shot could lower the barrier and vastly improve immunization rates.”

Vaccines that protect against multiple diseases have been used for decades, but no vaccine is currently approved that combines protection against the three major respiratory viruses that drive seasonal outbreaks: flu, COVID-19 and RSV.

The single-shot vaccine uses the same vaccine platform that Lovell has been developing for more than a decade. Dubbed “CoPoP,” it consists of tiny spherical nanoparticles made of cobalt and porphyrin with an outer shell of phospholipid. 

The platform works by attaching viral proteins to the nanoparticles via histidine tags – or his-tags. These short strings of amino acids have a natural affinity for metals, allowing them to form a strong bond with the cobalt ions in the nanoparticles. Once administered into the body through the vaccine, the viral proteins help train the immune system to recognize and defend against the viruses. 

For this study, Lovell’s team used CoPoP to package five viral proteins — three influenza proteins and proteins from SARS-CoV-2 and RSV — into a single vaccine. To make the vaccine more potent, they also added immune-boosting ingredients known as PHAD and QS-21 to the CoPoP platform.

“CoPoP is a really flexible formulation that allows multiple viral proteins to be incorporated at once,” Lovell says. 

CoPoP was also utilized for a COVID-19 vaccine candidate that advanced through phase 2 and phase 3 clinical trials in South Korea and the Philippines. That work was a partnership between UB spinoff company POP Biotechnologies, Inc. (POP BIO), co-founded by Lovell, and South Korean company EuBiologics.

Because it uses viral proteins rather than genetic instructions, the CoPoP approach differs from the most widely used COVID-19 vaccines, which rely on mRNA technology.

The team found no evidence of immune interference, in which one vaccine component reduces the immune response to another.

However, the researchers stress that additional studies are needed to determine whether subtle interactions among the different vaccine components could affect immune responses under different dosing conditions.

“We are hopeful that this platform could be expanded further to protect against an even wider range of respiratory viruses in the future,” Lovell says.