News|Articles|March 5, 2026

Researchers Reveal Universal Nasal Spray Vaccine With Broad Respiratory Protection

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Key Takeaways

  • An “infection-mimicking” design uses TLR4 and TLR7/8 agonists with OVA to drive lung-homing T cells and prolonged innate activation, aiming to bypass limitations of rapidly mutating respiratory antigens.
  • Three weekly intranasal doses lowered SARS-CoV-2 lung titers approximately 700-fold, enabled survival with minimal morbidity, and induced rapid virus-specific T-cell and antibody responses within 3 days of challenge.
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A single intranasal formulation demonstrated protection against SARS-CoV-2, bacterial pneumonia, and allergens for up to 3 months in preclinical models.

For decades, a truly universal vaccine capable of defending against virtually any respiratory pathogen has been considered unattainable. However, data from a Stanford Medicine preclinical trial published in Science describe an intranasal liposomal formulation, designated GLA-3M-052-LS+OVA, that protected mice against SARS-CoV-2 and other coronaviruses, including the hospital-acquired bacterial pathogens Staphylococcus aureus and Acinetobacter baumannii, and house dust mite allergens for at least 3 months following vaccination.1

Shifting From Antigen-Specific Vaccinology

Traditional vaccines work through antigen specificity. A recognizable pathogen component, such as the spike protein of SARS-CoV-2, is presented to the immune system so the body can quickly mount a targeted response upon reexposure. This model—which has guided vaccine development for years—wavers when pathogens mutate rapidly, necessitating reformulated annual flu shots and updated COVID-19 boosters each season.1

Rather than mimicking a specific pathogen, GLA-3M-052-LS+OVA mimics the cytokine signals exchanged by immune cells during an active infection, simultaneously engaging both the innate and adaptive arms of the immune system. The vaccine incorporates toll-like receptor (TLR) 4 and TLR7/8 agonists alongside ovalbumin, a model egg protein antigen that draws T cells into the lungs and sustains heightened innate immune activation for weeks to months.1,2

This mechanistic strategy builds on a 2023 finding from the same research group, in which the BCG tuberculosis vaccine was shown to mediate durable cross-protection in mice by keeping innate immune cells in the lungs persistently activated through T cell–derived cytokine signaling.1

Key Efficacy Findings

In mice receiving 3 intranasal doses 1 week apart, the vaccine reduced SARS-CoV-2 lung viral titers approximately 700-fold compared with unvaccinated controls. All vaccinated mice survived viral challenge with minimal weight loss, whereas unvaccinated animals experienced severe illness, extensive lung inflammation, and death.1-3

Notably, the vaccine accelerated the adaptive immune response as vaccinated mice mounted virus-specific T-cell and antibody responses within 3 days of viral challenge, compared with approximately 2 weeks in unvaccinated animals. This finding has potential implications for rapid pathogen containment.3

Further results demonstrated that protection extended beyond viruses and guarded against S aureus and A baumannii for approximately 90 days, pathogens of relevance given growing antibiotic resistance concerns in health care settings. The vaccine also substantially suppressed Th2-driven allergic responses, including mucus accumulation and eosinophil infiltration upon exposure to house dust mite allergens, suggesting a potential dual application in allergy prevention.1,3

Implications for Pharmacy Practice

The translational pathway ahead involves a phase 1 safety trial in humans. If results are favorable, senior author Bali Pulendran, PhD, a professor of microbiology and immunology at Stanford University in California, estimates that 2 intranasal doses could confer sufficient protection in individuals, with a clinically available product potentially reachable within 5 to 7 years with adequate funding.1,2

For pharmacists, this research carries near- and long-term relevance. In the immediate term, patients seeking annual respiratory vaccinations, including influenza, COVID-19, respiratory syncytial virus (RSV), and pneumococcal, require guidance on the current multiproduct landscape. Pharmacists serving as accessible, trusted immunization providers are uniquely positioned to counsel patients as the science evolves. Looking ahead, a single intranasal product offering broad seasonal protection could substantially simplify immunization schedules, reduce administration burden, and address hesitancy among needle-averse patients.

“Imagine getting a nasal spray in the fall months that protects you from all respiratory viruses, including COVID-19, influenza, RSV, and the common cold, as well as bacterial pneumonia and early spring allergens. That would transform medical practice,” Pulendran said in the news release.1

Although the findings remain preclinical and researchers themselves caution that current results are not a substitute for existing vaccines, the mechanistic clarity of the approach and the breadth of protection observed in animal models mark a meaningful inflection point in respiratory vaccine research.

REFERENCES
1. Zhang H, Floyd K, Fang Z, et al. Mucosal vaccination in mice provides protection from diverse respiratory threats. Science. Published online February 19, 2026. doi:10.1126/science.aea1260
2. Stanford Medicine. Scientists create universal nasal spray vaccine that protects against COVID, flu, and pneumonia. ScienceDaily. February 23, 2026. Accessed March 5, 2026. https://www.sciencedaily.com/releases/2026/02/260222092258.htm
3. Sheridan L. New research shows a single nasal spray could one day protect against COVID, the flu, pneumonia, and even asthma. Inc. March 4, 2026. Accessed March 5, 2026. https://www.inc.com/leila-sheridan/new-research-shows-a-single-nasal-spray-could-one-day-protect-against-covid-the-flu-pneumonia-and-even-asthma/91311713

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