For years, researchers have sought to develop a vaccine that can protect against any current or future influenza virus variants, including those that have the potential to cause pandemics. Such a universal flu vaccine could reduce serious influenza-related illness and possibly the need for an annual shot.

In May 2025, the Department of Health and Human Services (HHS) announced its support for a universal vaccine candidate designed to neutralize multiple influenza strains and provide “broad-spectrum protection against multiple strains of pandemic-prone viruses,” including coronaviruses and the H5N1 bird flu.

“The desire for a universal vaccine is strong in the scientific community and in the public health community,” said Mark Mulligan, MD, director of the Vaccine Center at New York University Langone, who is not involved with the HHS initiative.

“As a vaccine center director, I’m very happy that the director of HHS, who is known to be a vaccine skeptic, is supporting vaccine research, and particularly for a cause like this. And I hope that support will continue,” Mulligan told Verywell.

Why Do We Need a Universal Flu Vaccine?

Influenza mutates so quickly that the vaccine formula needs to be tweaked each year to protect against the three to four variants that scientists think will circulate most in the fall and winter.

Many Americans skip the vaccine—fewer than half of eligible people were vaccinated during the last flu season. When they do get it, the vaccine is about 20% to 60% effective at preventing hospitalization, depending on the year. The virus killed about 28,000 people in the 2023-24 flu season.

Creating a “variant-proof” vaccine for influenza and COVID could minimize some of the guesswork involved with updating the annual boosters. Mulligan said that if that vaccine were durable enough, people may not need to get the shot every year.

HHS Launches ‘Generation Gold Standard’ Program to Back Universal Flu Vaccine

The HHS is currently advancing two universal flu vaccine candidates, which both use a traditional vaccine-making technology.

In 2025, the Wall Street Journal reported that HHS is shifting $550 million away from COVID vaccine development programs to instead support the universal flu vaccine goal. The agency is giving an unspecified chunk of that money to support the work of two researchers who were recently named as directors of the National Institutes of Health (NIH) in an effort it dubbed “Generation Gold Standard.”

The HHS said the program “represents a decisive shift toward transparency, effectiveness, and comprehensive preparedness.” According to the Journal, there was no public call for applications, and it’s not clear why the pair’s project was chosen to receive the funding over other universal vaccine candidates.

The goal, said the agency, is to create a vaccine that wouldn’t have to be updated every year to match the viral strains of the moment. It also aims to protect against other respiratory viruses, including COVID and the H5N1 bird flu. The agency said the platform can be adapted for respiratory syncytial virus (RSV) and others.

“Generation Gold Standard is a paradigm shift,” Jay Bhattacharya, NIH director, said in a statement. “It extends vaccine protection beyond strain-specific limits and prepares for flu viral threats—not just today’s, but tomorrow’s as well—using traditional vaccine technology brought into the 21st century.”

The HHS said clinical trials for the vaccine are set to begin in 2026, with the goal of getting FDA approval by 2029. An intranasal universal flu vaccine using the same technology is already in advanced testing and is also slated for FDA review in 2029. The agency said that the goal of that formulation is to “block virus transmission” by delivering the vaccine into the nose.

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How the HHS-Funded Universal Flu Vaccine Will Work

The NIH-developed vaccine is comprised of a mix of four whole influenza viruses that have been killed using a chemical called beta-propiolacton (BPL). This process ensures the viruses can’t cause illness but still carry enough recognizable features to train the immune system to respond if a similar virus ever invades the body in the future.

BPL-inactivated whole virus technology has been around for 80 years, said Kirsten Hokeness, PhD, director of the School of Behavioral Health and Science at Bryant University.

“Many prior uses or past clinical trials of these preps showed the need for multiple boosters to maintain immunity. Unlike newer technologies, there are also concerns about scalability given the need for specialty facilities to produce them,” Hokeness told Verywell in an email.

Mulligan said that inactivated whole virus vaccines are “old school,” but still effective and worth exploring. They are also easier and cheaper to store than mRNA and other vaccine types.

Inactivated virus vaccines induce essential immune cells, including helper T cells, B cells, and antibodies. However, Mulligan said, they don’t induce ACD-8 or killer T cells, which may or may not be necessary for a universal vaccine to be effective. That’s something only clinical trials can determine.

“It’s important to support a variety of approaches and not put all your eggs in one basket. It certainly would not be appropriate, in my view, to be supporting only a whole-kill virus platform as a universal vaccine research program,” Mulligan said. “We need to have multiple irons in the fire and test candidates in parallel.”

Jury’s Still Out on the Best Vaccine Technology

In a statement to Verywell, the HHS said the BPL-inactivated virus vaccine is the first in the Generational Gold Standard line-up, but that it plans to support other approaches, too.

“NIH looks forward to working with many different researchers with novel ideas beyond mRNA and other failed strategies of the past in preventing transmission of these important respiratory pathogens,” the HHS said. Clinical trials have repeatedly proven the safety and effectiveness of mRNA vaccines, including for COVID and various cancers.

There are 42 other universal vaccine candidates that are being tested in clinical trials, including seven that are designed to neutralize both flu and COVID. Many of those use more modern vaccine technology, such as mRNA, viral vector, and DNA platforms.  

Most vaccine types work by introducing the body to bits of the outer protein of influenza viruses rather than the whole virus. Some experimental mRNA vaccines, for instance, can introduce the immune system to 20 different viruses. Achieving that breadth of coverage could mean a vaccine is protective against future seasonal influenza strains as well as viruses with pandemic potential, like H5N1.

Several influenza viruses carry proteins in the same place. Some vaccine candidates target those “conserved regions” to try to protect against multiple viruses.

“It’s important to support a variety of approaches and not put all your eggs in one basket. It certainly would not be appropriate, in my view, to be supporting only a whole-kill virus platform as a universal vaccine research program,” Mulligan said. “We need to have multiple irons in the fire and test candidates in parallel.”