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Since the coronavirus enters the body through the nose, researchers have figured a nasal spray may be one way to defend against its spread. But developing an effective point-of-entry vaccine can be elusive—even for companies that are able to throw the most money at the job.

On Tuesday, AstraZeneca’s researchers at the University of Oxford said their nasal vaccine candidate came up short in a phase 1 trial, failing to produce a strong immune response in the nasal mucosa of a majority of recipients. The spray also elicited weaker systemic immune responses than intramuscular vaccines.

The spray is a version of AZ’s adenovirus COVID-19 shot Vaxzevria. AZ had hoped that it could quickly develop it similarly to its spray vaccine Flumist, which defends against the flu.

Despite AZ’s troubles, Bharat Biotech of India and CanSino Biologics of China have scored approvals in their respective countries for their nasal COVID-19 vaccines.

The AZ-funded trial enrolled 30 unvaccinated people. It also weighed the value of the spray as a booster, testing it on 12 individuals who had previously been vaccinated with a standard two-shot injection.

“The nasal spray did not perform as well in this study as we had hoped,” Oxford professor and the trial’s chief investigator Sandy Douglas said in a statement. “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.”

In attempting to explain the failure, Douglas suggested that much of the spray could end up being swallowed and destroyed in the stomach. Ideally, the vaccine would be delivered directly into the lungs.

Douglas also said a new formulation designed specifically to be inhaled might be the answer. In using the same formula as that in Vaxzevria, AZ had hoped it would allow for rapid approval by regulators.

“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,” Douglas concluded.