Thirty volunteers will take part in the trial to test the immune response through the nose.
Scientists are to look into the effectiveness of the Oxford/AstraZeneca vaccine when delivered using a nasal spray.
The University of Oxford will examine the level of immune system responses generated by the vaccine using this delivery technique, as well as monitoring safety and for any adverse reactions.
Thirty healthy Oxford-based volunteers aged 18-40 will receive the vaccine through an intranasal spray device, similar to many over-the-counter hay fever nasal sprays.
The Oxford-AstraZeneca jab is currently being delivered by intramuscular injection as part of the national rollout.
Dr Sandy Douglas, who is leading the study, said: “Some immunologists believe that delivering the vaccine to the site of infection may achieve enhanced protection, especially against transmission, and mild disease.
“We hope this small safety-focused study will lay the foundation for future larger studies that are needed to test whether giving the vaccine this way does protect against coronavirus infection.”
Dr Douglas added: “There are a variety of people who will find an intranasal delivery system more appealing, which may mean vaccine uptake is higher in those groups.
“It might also have practical advantages – nasal sprays have been used successfully for other vaccines, for example the flu vaccine used in UK schools.”
Dr Meera Madhavan, lead clinical research fellow at the Jenner Institute, said: “This study will help us to understand the safety of, and side-effects associated with, giving the Oxford/ AstraZeneca Covid-19 vaccine by nasal spray.
“It is an important first step towards increasing our range of options for curtailing the spread and impact of Covid-19 globally.”
Professor Adrian Hill, director of the Jenner Institute, said the results could how effective the vaccine is in preventing disease episodes and asymptomatic infections, possibly helping to reduce transmission.