Stanford Researchers Announce Potential ‘Universal’ Vaccine Offering Broad Protection Against Respiratory Infections

For decades, scientists have pursued the elusive goal of a universal vaccine capable of protecting against a wide range of infectious threats. Now, researchers at Stanford Medicine and their collaborators have taken a significant step toward realizing that vision. A modern study in mice demonstrates that an experimental universal vaccine shields against various respiratory viruses, bacteria, and even allergens.

The vaccine, administered intranasally – such as through a nasal spray – provides broad protection in the lungs that lasts for months. The findings, published February 19, 2026, in Science, show that vaccinated mice were protected from SARS-CoV-2 and other coronaviruses, Staphylococcus aureus and Acinetobacter baumannii (common hospital-acquired infections), as well as house dust mites (a common allergen). According to Bali Pulendran, PhD, the Violetta L. Horton Professor II and professor of microbiology and immunology, the level of protection across so many respiratory threats exceeded expectations. Stanford Medicine News

The study’s lead author is Haibo Zhang, PhD, a postdoctoral scholar in Pulendran’s lab.

If similar results are achieved in humans, a single vaccine could potentially replace multiple yearly shots for seasonal respiratory illnesses and provide rapid protection if a new pandemic virus emerges.

A Departure from Traditional Vaccine Strategies

This experimental vaccine operates differently from traditional vaccines. Since the late 1700s, when Edward Jenner pioneered vaccination using cowpox to prevent smallpox, vaccines have relied on antigen specificity. This means vaccines present the immune system with a recognizable piece of a pathogen – such as the spike protein on SARS-CoV-2 – so the body can quickly identify and attack the real virus later. BBC News

“That’s been the paradigm of vaccinology for the last 230 years,” Pulendran said. Stanford Medicine News

A key challenge with this approach is that many pathogens evolve rapidly. When viruses change the structures on their surface, previously effective vaccines may lose potency, necessitating updated COVID-19 boosters and annual flu shots. Stanford Medicine News

“It’s becoming increasingly clear that many pathogens are able to quickly mutate. Like the proverbial leopard that changes its spots, a virus can change the antigens on its surface,” Pulendran said. Stanford Medicine News

Activating Integrated Immunity

Instead of mimicking a part of a virus or bacterium, this new vaccine imitates the communication signals immune cells exchange during infection. By doing so, it links the body’s two main defense systems – innate and adaptive immunity – into a coordinated and longer-lasting response. BBC News

Most existing vaccines primarily stimulate the adaptive immune system, which produces antibodies and specialized T cells that target specific pathogens and retain memory for years. The innate immune system responds within minutes of infection and acts more broadly, deploying cells such as dendritic cells, neutrophils and macrophages that attack perceived threats. However, innate immunity typically fades within days.

Pulendran’s team focused on the innate system’s versatility. “What’s remarkable about the innate system is that it can protect against a broad range of different microbes,” Pulendran said. Stanford Medicine News

The researchers found that T cells recruited to the lungs as part of the adaptive response were sending signals that kept innate immune cells switched on, extending the innate response for months. Stanford Medicine News

They identified the T cell signals as cytokines that activate pathogen sensing receptors called toll-like receptors on innate immune cells. Stanford Medicine News

How the Nasal Vaccine Works

The new formulation, currently called GLA-3M-052-LS+OVA, is designed to replicate the T cell signals that stimulate innate immune cells in the lungs. It also includes a harmless antigen, an egg protein known as ovalbumin or OVA, which draws T cells into the lungs and helps sustain the boosted innate response for weeks to months. Stanford Medicine News

In the study, mice received the vaccine as droplets placed in their noses. Vaccinated mice were protected from SARS-CoV-2 and other coronaviruses for at least three months. Stanford Medicine News

Unvaccinated mice experienced severe weight loss and often died, while vaccinated mice lost far less weight, all survived, and their lungs contained little virus. The sustained innate response reduced viral levels in the lungs by 700-fold. Stanford Medicine News

“The lung immune system is so ready and so alert that it can launch the typical adaptive responses – virus-specific T cells and antibodies – in as little as three days, which is an extraordinarily short length of time,” Pulendran said. “Normally, in an unvaccinated mouse, it takes two weeks.” Stanford Medicine News

The vaccine also protected against Staphylococcus aureus and Acinetobacter baumannii, and reduced allergic reactions to house dust mites. Stanford Medicine News

What’s Next?

The next step is human testing, beginning with a Phase I safety trial. If those results are positive, larger studies would follow, potentially including controlled exposure to infections. Pulendran estimates that two doses delivered as a nasal spray could be sufficient for people. Stanford Medicine News

With adequate funding, he believes a universal respiratory vaccine could become available within five to seven years, potentially strengthening defenses against future pandemics and simplifying seasonal vaccination. Stanford Medicine News

“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.” Stanford Medicine News