Researchers at Stanford Medicine have created an experimental nasal spray vaccine that protects mice against multiple respiratory threats, including COVID-19, flu, bacterial pneumonia, and allergens. The vaccine activates the lungs' innate immune system for months, offering broad defense without targeting specific pathogens. Published in Science on February 19, the study suggests potential for human trials soon.
Scientists at Stanford Medicine, in collaboration with researchers from Emory University, the University of North Carolina at Chapel Hill, Utah State University, and the University of Arizona, have developed a novel intranasal vaccine aimed at providing wide-ranging protection against respiratory illnesses. Unlike traditional vaccines that rely on antigen specificity to target particular viruses or bacteria, this approach—named GLA-3M-052-LS+OVA—mimics immune cell signals to link innate and adaptive immunity, sustaining heightened lung defenses for months.
The study, led by Haibo Zhang, PhD, a postdoctoral scholar, and senior author Bali Pulendran, PhD, the Violetta L. Horton Professor II of microbiology and immunology, was published on February 19 in Science. In experiments, mice received the vaccine via nasal droplets, with some getting multiple doses one week apart. Vaccinated mice exposed to SARS-CoV-2 and other coronaviruses showed reduced viral levels by 700-fold, minimal weight loss, and survival rates of 100%, compared to unvaccinated mice that suffered severe illness and high mortality. Protection lasted at least three months.
The vaccine also shielded against bacterial infections from Staphylococcus aureus and Acinetobacter baumannii, common in hospitals, and mitigated allergic responses to house dust mite proteins by weakening Th2 immune reactions and reducing airway mucus. Pulendran noted, "The lung immune system is so ready and so alert that it can launch the typical adaptive responses... in as little as three days, which is an extraordinarily short length of time."
This builds on prior work showing how the Bacillus Calmette-Guérin tuberculosis vaccine extends innate immunity via T cell cytokines activating toll-like receptors. Funding came from the National Institutes of Health (grant AI167966), the Violetta L. Horton Professor endowment, the Soffer Fund endowment, and Open Philanthropy.
Next steps include a Phase I safety trial in humans. Pulendran estimates two doses could suffice, potentially leading to availability in five to seven years. He envisions it protecting against COVID-19, influenza, respiratory syncytial virus, common colds, bacterial pneumonia, and spring allergens, transforming respiratory health care.
