A team at Duke-NUS Medical School in Singapore has developed a nasal COVID-19 vaccine that outperforms standard injections in two key ways: it triggers a stronger immune response and offers longer-lasting protection — even against new and emerging variants. The findings raise the prospect of a future where fewer booster shots are needed to keep vulnerable people safe.
At a glance
- Intranasal vaccine: The new candidate is delivered directly into the nose, targeting the mucosal surface where SARS-CoV-2 first enters the body.
- T cell response: Nasal delivery produced more T central memory cells than standard injections, which researchers say could translate to longer-lasting protection.
- Variant neutralization: IgG antibodies triggered by intranasal vaccination were more effective at neutralizing newly emerging variants than those produced by conventional shots.
Why the nose?
SARS-CoV-2 enters the body through the mucosal surfaces of the nasal passages and lung airways. Delivering a vaccine right at that entry point is a logical strategy — and the data backs it up.
In tests on hamsters, the intranasal vaccine boosted antibody activity in the mucosa while also producing distinct effects on T cells compared to subcutaneous injection. Most notably, it preferentially stimulated airway-resident T cells and central memory T cells — immune cells that sit ready to mount a defense when the body encounters the virus again. Animals vaccinated through the nose had more of these cells, and those cells produced stronger cytokine responses, meaning a more forceful immune reaction when needed.
Cytokines are small proteins that regulate the activity of other immune cells. A bigger cytokine response generally means a more coordinated and effective immune defense.
Fewer boosters, broader protection
One of the most promising aspects of the research is what it could mean for booster schedules. Current COVID-19 vaccines provide meaningful protection, but that protection wanes over time, which is why regular boosters have become part of the vaccination landscape for many people — particularly the elderly and immunocompromised.
By generating larger populations of central memory T cells, the intranasal approach could extend the window of protection significantly. “Our data show that, compared to subcutaneous vaccination, the intranasal route improved the response of certain immune cells, known as T cells, which reduced disease severity,” said Ashley St. John, the study’s corresponding author. “Not only that, but it also resulted in a greater number of T central memory cells compared to subcutaneous vaccination, which could lead to longer-lasting protection.”
Co-author Patrick Tan pointed to the continued emergence of new variants as a reason to keep refining the tools available. “This study shows that mucosal vaccination holds promise for improving COVID-19 vaccine efficacy with potentially fewer boosters needed,” he said.
The role of adjuvants
The research team also found that adjuvants — substances added to vaccines to strengthen the immune response — played a meaningful role in shaping how T cells behaved. Different adjuvants produced different T cell profiles, suggesting that the formulation of the vaccine can be tuned to optimize specific aspects of immunity. This opens a line of research into which adjuvant combinations work best for mucosal delivery against respiratory pathogens.
The vaccine also boosted immunoglobulin G, or IgG — the most common antibody in the human body, responsible for fighting bacterial and viral infections. When induced through intranasal vaccination, IgG showed greater effectiveness at neutralizing viral variants, including newly emerging ones, compared to injection-induced IgG. That broader neutralizing capacity is significant, given how quickly SARS-CoV-2 has continued to evolve.
What comes next
Duke-NUS has filed a patent covering the intranasal vaccine composition, paving the way for an industry partnership that could move the candidate toward clinical development. The patent covers not just COVID-19 applications but also other pathogens that target mucosal surfaces — meaning this research could eventually inform vaccines for influenza, respiratory syncytial virus, and other airborne threats.
The study was published in the journal eBioMedicine, a peer-reviewed open-access journal published by The Lancet group. Current findings are based on animal studies, so human clinical trials will be the next critical step before the vaccine could be considered for approval or widespread use.
That gap between animal studies and proven human efficacy is a real one, and it means the timeline to a widely available intranasal COVID-19 vaccine remains uncertain. Still, the mechanistic evidence from this research is clear: delivering a vaccine where the virus actually enters the body appears to give the immune system a meaningful head start.
Singapore’s Duke-NUS Medical School has become an important center for infectious disease research in Southeast Asia, a region that has experienced the pressures of emerging viral threats acutely. This work builds on a broader body of research into mucosal immunity that has gained momentum since the COVID-19 pandemic accelerated vaccine science globally. Several other research groups are also pursuing nasal vaccine candidates, suggesting this field is maturing quickly.
For communities where booster fatigue is a genuine barrier to keeping vaccination rates high, a longer-lasting option delivered without a needle could make a real difference in public health outcomes.
Read more
For more on this story, see: New Atlas
For more from Good News for Humankind, see:
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- The Good News for Humankind archive on Singapore
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