Picture this: the next time a pandemic strikes, instead of lining up for shots, people could simply spray a vaccine up their nose at home. No needles, no pain—just a quick sniff and you are protected. Such is the future that researchers like Yi Yan Yang, a Distinguished Principal Scientist at the A*STAR Bioprocessing Technology Institute (A*STAR BTI), are working toward today.
Vaccines based on messenger RNA (mRNA) technology were critical to protecting people from COVID-19 infections and staving off the spread of the disease. Future pandemic responses may become even easier with nasal vaccines, such as the one being developed by Yang and her team at A*STAR BTI, together with collaborators from A*STAR Infectious Diseases Labs (A*STAR ID Labs), A*STAR Genome Institute of Singapore (A*STAR GIS) and National University of Singapore.
“This would enable easier mass vaccination and self-administration, which is going to be valuable for large-scale immunisation campaigns,” Yang explained. But there’s a catch—the nose’s mucus barrier acts like a bouncer at an exclusive club, keeping foreign materials out.
To sneak mRNA vaccines past this mucosal defence system, the researchers thought of creating tiny ‘invisibility cloaks’ by redesigning the lipid nanoparticles (LNPs) that carry the mRNA molecules.
Unlike the rigid, crystalline particles used in needle-based SARS-CoV-2 mRNA vaccines, the team built flexible particles using triolein, a lipid that stays liquid at body temperature. Think of it like the difference between trying to squeeze a marble versus a water balloon through a tight space—the flexible option triumphs. The team also fine-tuned these liquid-core LNPs to match the pH levels of the mucus barrier, preventing them from clumping or breaking down in the nasal environment.
“Our best-performing LNP formula delivered mRNA 60 times more effectively than the commercial lipid nanoparticles when sprayed into mice noses,” said Yang. Even better, the liquid particles caused less inflammation than traditional formulations, which could potentially reduce the side effects like fever and fatigue.
Nasal vaccine delivery offers another advantage: it promotes immunity right where respiratory viruses enter the body, forming a shield at the front door in addition to preparing the body’s internal defences.
To optimise their liquid lipid recipe further, Yang and the team are testing further LNP formulations and vaccine dosage levels to strengthen the protective immune response that it can elicit in the respiratory tract. Their innovation could transform how we prepare for future pandemics—making immunisation as simple as breathing.
The A*STAR-affiliated researchers contributing to this research are from the A*STAR Bioprocessing Technology Institute (A*STAR BTI), A*STAR Infectious Diseases Labs (A*STAR ID Labs), and the A*STAR Genome Institute of Singapore (A*STAR GIS)
