The nasal spray vaccine being developed by scientists at Oxford University only triggers mucosal antibody responses in a minority of people, according to the first data available from its phase 1 clinical trial.
The mucosal immune system is the largest component of the entire immune system, involving the lining of parts of the body such as the nose, mouth, lungs and stomach. Some experts believe that achieving immunity at these sites could help to prevent mild cases of COVID-19, as well as reducing transmissibility.
The majority of studies of immune responses to COVID-19 have focused on serum antibodies and systemic, cell-mediated immunity. In this study, systemic immune responses to the nasal spray vaccine were also weaker compared with intramuscular injection of the vaccine.
The study, published in the journal eBioMedicine, was undertaken at Oxford University in collaboration with AstraZeneca, and used the same AstraZeneca vaccine that is already licensed for use by injection, so that rapid rollout would be possible should the results be positive.
The trial enrolled 30 previously unvaccinated participants to receive a primary dose of the nasal spray vaccine. The researchers also studied the feasibility of the vaccine as a booster in 12 participants who had previously received a standard two-dose COVID-19 vaccine schedule by injection.
The researchers had hoped that a simple nasal spray might be a more practical option for large-scale vaccine campaigns than a more complex nebuliser device, such as that used for a COVID-19 vaccine recently licensed in China. Some researchers believe a nasally administered vaccine could be more effective in generating immunity in the airways themselves, something that vaccines by injection have so far been less effective at achieving.
A possible next step may be 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.
No serious adverse events or safety concerns were reported during the trial.
Dr Adam Ritchie, Senior Vaccine Programme Manager at the University of Oxford, 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.
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.