Edinburgh team to test intranasal interferon add-on with vaccines to boost nasal immunity and cut spread

Respiratory infections remain a major global burden, yet most licensed vaccines against these pathogens are delivered intramuscularly and chiefly induce systemic immunity. Protection at the upper respiratory tract—the nose and upper airways, where many infections begin—remains limited.

Aside from the paediatric flu nasal spray, few approaches actively prime the nasal mucosa, which helps explain why vaccinated individuals can still acquire infection and transmit it.

University of Edinburgh researchers led by Dr Rupsha Fraser from Edinburgh Medical School and Centre for Inflammation Research, have developed a non‑antigenic adjunct that separates antigen delivery from local immune conditioning.

The concept is to administer a standard intramuscular vaccine and co-administer a brief intranasal dose of interferon‑alpha (IFN‑α). This is designed to trigger an interferon‑driven immunomodulatory programme in the nasal mucosa, recruit vaccine‑specific lymphocytes and establish local immune readiness without placing vaccine antigen in the nose, which in humans is hampered by rapid mucociliary clearance.

In animal studies, intranasal IFN‑α given concurrently with parenteral vaccination directed antigen‑specific CD4+ and CD8+ T cells to the upper respiratory tract, indicating that mucosal immunity can be induced in an antigen‑independent manner to localise vaccine responses.

This work, conducted with the AstraZeneca SARS‑CoV‑2 vaccine, is available as a preprint. With that platform no longer in clinical use the team has pivoted to using PnuBioVax, a novel protein-based vaccine for pneumococcal disease.

The team will define an immunologically relevant dose range for testing, manufacture and release a clinical-grade product suitable for human use, and conduct a dose-ranging study in humans to identify an optimal dose range for this purpose i.e. the dose that produces the intended biological response in the nose within defined tolerability criteria. 

Subsequent clinical trials will test whether coadministration of intranasal IFN-α with intramuscular vaccination directs vaccine-induced immune responses to the nasal lining, where infection begins, by measuring local immune responses in the nose and assessing effects on infection acquisition. The researchers plan to include their evaluation alongside existing and investigational vaccines, including controlled human infection model trials in Africa.

Further in the future, there are plans to advance this strategy to commercialisation through scalable manufacture of the intranasal IFN- product and partnership with vaccine developers, enabling integration with existing and new vaccines for broad application across vaccination programmes. 

By providing a practical route to immune control at the site of pathogen entry, this adjunct could reduce infection and transmission, strengthen protection for vulnerable groups and offer a scalable, platform‑agnostic tool for pandemic preparedness that can be layered onto current vaccination programmes.

Rupsha Fraser

Centre for Inflammation Research

Edinburgh Medical School

World Immunisation Week