Stanford Researchers Develop Universal Nasal Spray Vaccine Against Respiratory Threats

A single nasal spray may offer broad protection against a wide range of respiratory illnesses, including COVID-19, influenza, bacterial pneumonia, and even allergies, according to a new study in mice. Researchers at Stanford Medicine have developed an experimental vaccine that, when administered as a nasal spray, demonstrated widespread protection in the lungs for several months.

The research, published on February 19 in the journal Science, represents a significant step toward a “universal” vaccine – a long-sought goal in medical research. Currently, vaccines rely on “antigen specificity,” meaning they target a specific component of a pathogen to prepare the immune system. This approach, while effective, requires frequent updates to address viral mutations, as seen with annual influenza vaccines and the ongoing need for updated COVID-19 boosters.

“This has been the paradigm of vaccinology for the last 230 years,” explained Bali Pulendran, PhD, professor of microbiology and immunology at Stanford Medicine and senior author of the study. “Since the 1790s, when Edward Jenner pioneered vaccination, all subsequent vaccines have relied on the same fundamental principle.”

The new vaccine takes a different tack. Instead of mimicking specific parts of viruses or bacteria, it works by amplifying the lungs’ natural defenses. It essentially mimics the signals exchanged between immune cells during an infection, coordinating both the innate and adaptive immune responses. The innate immune system provides a rapid, non-specific defense, while the adaptive immune system learns to recognize and target specific pathogens.

“What’s remarkable about the innate system is that it can protect against a broad variety of different microorganisms,” Dr. Pulendran stated. The researchers built upon previous observations from studies with the BCG vaccine for tuberculosis, which showed evidence of prolonged, cross-protective immunity. They found that certain immune cells were sustaining activation of the innate immune system for an unusually long period – up to three months.

The new formulation, designated GLA-3M-052-LS+OVA, is designed to replicate these signals and keep the lung’s immune system on high alert. In the mouse study, three doses of the vaccine, delivered as nasal drops, provided protection against SARS-CoV-2 and other coronaviruses for at least three months. The vaccine significantly reduced viral levels in the lungs – by 700-fold, according to the study.

“The pulmonary immune system is so primed and so alert that it can unleash the typical adaptive responses – virus-specific T cells and antibodies – in as little as three days,” Dr. Pulendran explained. “Normally, in a non-vaccinated mouse, that takes two weeks.”

Beyond viruses, the vaccine also demonstrated protection against common respiratory bacteria. When mice were exposed to allergens like house dust mites, vaccinated animals exhibited a significantly reduced inflammatory response and preserved airway function. “I think what we have is a universal vaccine against a variety of respiratory threats,” Dr. Pulendran said.

The researchers are now preparing to initiate Phase 1 clinical trials to assess the safety of the vaccine in humans. If those trials are successful, larger studies will follow. Dr. Pulendran estimates that, with adequate funding, a universal respiratory vaccine could be available within five to seven years.

“Imagine receiving a nasal spray in the fall that protects you against all respiratory viruses, including COVID-19, influenza, respiratory syncytial virus, and the common cold, as well as bacterial pneumonia and spring allergens,” Dr. Pulendran envisioned. “That would transform medical practice.”

The development of this vaccine represents a shift in thinking about how to combat respiratory illnesses. Rather than chasing constantly evolving pathogens with targeted vaccines, this approach aims to bolster the body’s inherent defenses, providing a broader and more durable shield against a wide range of threats. Further research and clinical trials will be crucial to determine whether this promising approach translates to effective protection in humans.

According to a report from February 23, 2026, the World Health Organization recently declared the end of the global health emergency for COVID-19, signaling a transition in the management of the virus. However, the ongoing threat of respiratory infections underscores the need for innovative preventative measures like this universal vaccine candidate.