Intranasal COVID-19 vaccine candidate’s clinical data highlights need for further development of nasal spray vaccines

11 October 2022

Researchers from the University of Oxford have today reported new findings from a Phase 1 clinical trial studying the safety and immune response of an intranasally-administered vaccine against COVID-19.
The study was performed at the University in collaboration with AstraZeneca and used the same vaccine based on the ChAdOx1 adenovirus vector, as is already licensed for use by injection.

In their findings (published in eBioMedicine), the researchers reported mucosal antibody responses were seen in a minority of participants. Systemic immune responses to intranasal vaccination were also weaker compared with intramuscular vaccination. Therefore, the vaccine did not generate a consistent mucosal antibody nor a strong systemic immune response. No serious adverse events or safety concerns were reported during the trial.

The new Oxford study is thought to be the first to have published data from administration of an adenovirus-vectored vaccine using a simple nasal spray, which might be a more practical option for large-scale vaccine campaigns than a more complex nebuliser device – such as that used by a COVID-19 vaccine recently licensed in China – say the researchers.

Dr Adam Ritchie, Senior Vaccine Programme Manager, said:
‘Delivering vaccines to the nose and airways is one of the most promising ways to achieve immunity within the airways, which could stop mild COVID infections and transmission of the virus more effectively than injected vaccines.
‘It also has the advantage of avoiding use of a needle. Many parents will know that nasal sprays are already used for the flu vaccine offered to schoolchildren in some countries, including the UK.’

The ChAdOx1 vector used in the vaccine is a weakened version of a common cold virus (adenovirus) that has been genetically modified so it is impossible for it to replicate in humans. The trial enrolled 30 previously unvaccinated participants to receive a primary dose of the intranasal vaccine. Additionally, the researchers studied the feasibility of the intranasal vaccine as a booster – 12 participants, who had previously received a standard two-dose COVID-19 vaccine schedule by injection, were administered the intranasal vaccine.

Associate Professor Sandy Douglas, Chief Investigator of the trial at the Jenner Institute, University of Oxford, said:
‘The nasal spray did not perform as well in this study as we had hoped. This was quite different from recent data from China, which has suggested good results can be achieved by delivery of a similar vaccine deep into the lungs with a more complex nebuliser device. A nasal spray vaccine similar to ours has recently been approved for intranasal use in India and we are looking forward to the peer-reviewed publication of the clinical trial data used to support that.
‘We believe that delivery of vaccines to the nose and lungs remains a promising approach, but this study suggests there are likely to be challenges in making nasal sprays a reliable option.
‘One possibility is simply that the majority of the nasal spray vaccine ends up being swallowed and destroyed in the stomach – delivery to the lungs could avoid that. A further challenge is that researchers don’t fully understand the relationships between the strength and types of immune responses within the airways and protection against infection.
‘We urgently need more research to develop vaccines which can block transmission of respiratory pandemic viruses using delivery routes which are safe and practical at large scale.’

For this study, researchers wanted to use exactly the same vaccine as the Oxford-AstraZeneca one to facilitate rapid rollout if the results were positive.

They say a possibility for the future is to develop formulations tailor-made for nasal spray use, for example using higher concentrations or using substances designed to help the vaccine stick in the nose rather than being swallowed. Encouraging safety data from this study would help such future work.

The study was funded by AstraZeneca.

Notes for editors

Link to the paper (will only go live once embargo lifts) -

For further information, a copy of the paper or to request an interview with the researchers, please contact: [email protected] or call 01865 280528.

About the Jenner Institute
The Jenner Institute is based within the Nuffield Department of Medicine, University of Oxford, and is headquartered at the Old Road Campus Research Building, in Headington, Oxford. The Jenner Institute also supports senior vaccine scientists, known as Jenner Investigators, within many other departments across the University of Oxford, as well as externally within The Pirbright Institute and the Animal and Plant Health Agency.
The Jenner Institute brings together investigators who are designing and developing numerous vaccines to generate an exceptional breadth of scientific know-how and critical mass, whilst still allowing the individual investigators to remain independent and accountable to their funders and stakeholders.
The Jenner Institute is supported by the Jenner Vaccine Foundation, a UK registered charity and is advised by the Jenner Institute Scientific Advisory Board.

About the University of Oxford
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