Universal vaccine could protect against flu, COVID-19 and colds, say researchers
A new nasal spray vaccine works by prepping the immune system’s broadest defence system against a range of potential new threats.
- 26 March 2026
- 5 min read
- by Priya Joi
At a glance
- An experimental vaccine protected mice against multiple respiratory threats, including flu, coronaviruses, cold viruses and bacterial pneumonia by triggering a broad immune defence rather than targeting a single pathogen.
- The new approach reduced viral loads dramatically and prevented severe lung disease in vaccinated animals.
- The findings are an early proof of concept and haven’t yet been tested in larger animals or people, but could pave the way for a universal respiratory vaccine that avoids multiple annual boosters to target mutating strains.
Early studies of a new single nasal spray vaccine suggest it could protect against all respiratory viruses, including COVID-19, influenza and the common cold, as well as bacterial lung infections and even allergies, according to researchers.
The vaccine, tested in mice and published in the journal Science, represents what scientists have been chasing for decades: a universal shot that guards against multiple respiratory threats without needing updates every time a pathogen mutates.
If it works in humans, it could replace the annual cycle of flu shots and COVID-19 boosters and provide a ready defence against the next pandemic.
“I think what we have is a universal vaccine against diverse respiratory threats,” said Bali Pulendran, a professor of microbiology and immunology at Stanford Medicine who led the research.
Breaking the cycle
What makes the team’s approach revolutionary is that it abandons how vaccines have typically worked for more than two centuries.
Every vaccine since the 1790s has relied on antigen specificity: mimicking a distinctive piece of a pathogen to prepare the body to recognise that exact threat.
Pathogens and vaccine-makers have been at war ever since. The pathogen evolves to evade the immunity triggered by the vaccine, the vaccine is changed to attack the new version of the pathogen, the pathogen mutates again and so on.
This is why we need new flu shots every year and why COVID-19 vaccines need updating as the virus mutates.
Pulendran’s team decided not to target specific pathogens. Instead, they wanted to imitate the way immune cells communicate with each other to ready the body’s defences during an infection.
They developed a vaccine that amplifies the immune system’s natural ability to respond to whatever threatens the lungs, whether viral, bacterial or allergic.
Two systems
Most vaccines target the adaptive immune system. This is the body’s precision weapon, producing antibodies and specialised cells called T cells that are custom-built to attack specific invaders.
Adaptive immunity has an excellent memory; it can recognise a pathogen years after first exposure. But it’s slow: mounting a full adaptive response typically takes two weeks, and it’s specific to a single pathogen.
The innate immune system is different. It’s made up of generalist cells such as macrophages, neutrophils and dendritic cells that attack anything they identify as dangerous. Innate immunity activates within minutes and can handle diverse threats, but was thought to be too short-lived for a vaccine.
Pulendran’s team asked: what if innate immunity could be made to last?
The idea came from research Pulendran’s team did in 2023 on the BCG tuberculosis vaccine, one of the world’s most widely used shots. Studies had suggested it might protect infants against infections beyond TB, but no one understood how.
Pulendran’s lab found that T cells recruited to the lungs as part of the adaptive response were sending chemical messages to innate immune cells, keeping them active for months instead of days.
The new vaccine that Pulendran’s team tested, called GLA-3M-052-LS+OVA, mimics that messaging process synthetically. It contains compounds that directly stimulate innate immune cells in the lungs, putting them on high alert. It also includes a harmless protein antigen – ovalbumin, from eggs – that draws T cells into the lungs. Those T cells then sustain the innate response through their own cytokine signals.
Nasal protection
In this study, mice were given GLA-3M-052-LS+OVA as a nasal vaccine, with some getting multiple doses a week apart. Each mouse was then exposed to one type of respiratory virus. Three doses of the vaccine protected the animals against SARS-CoV-2 and other coronaviruses for at least three months.
Unvaccinated mice by contrast became very sick. They had severe lung inflammation, high viral loads and often died. Vaccinated mice all survived and their lungs were nearly clear of the virus.
Then the research team tested bacteria: Staphylococcus aureus and Acinetobacter baumannii, both major causes of hospital-acquired pneumonia. Again, vaccinated mice were protected.
Finally, they tried allergens. Mice exposed to house dust mite protein, a major asthma trigger, normally develop inflamed, mucus-clogged airways. Vaccinated mice’s airways remained clear.
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Dual effect
What makes the vaccine work is its dual effect on respiratory defenses. The innate response that’s triggered causes a heightened state of alert in the lungs that slashes viral loads by 700-fold. Second, it accelerates the body’s ability to mount a targeted counterattack, cutting response time from two weeks down to three days.
The researchers say that even if the virus “slips through the net” of the innate response, it will be met with a strong adaptive response.
The next step is human trials. Pulendran’s team hopes to begin with safety testing, followed by controlled exposure studies if the vaccine proves safe. He estimates two nasal spray doses would probably be sufficient for humans.
“Imagine getting a nasal spray in the fall months that protects you from all respiratory viruses including COVID-19, influenza, respiratory syncytial virus and the common cold, as well as bacterial pneumonia and early spring allergens,” Pulendran said. “That would transform medical practice.”
