Hopes of distributing the Oxford/AstraZeneca Covid vaccine as a nasal spray have been dealt a blow after researchers said it performed poorly in its first clinical trial.
The underwhelming results have led scientists to abandon plans to develop the spray in its current form, with hopes now resting on different formulations of the vaccine and more complex delivery devices, such as nebulisers that can deliver medicines deep into the lungs.
“The nasal spray did not perform as well in this study as we had hoped,” said Dr Sandy Douglas, the chief investigator on the trial at Oxford’s Jenner Institute. “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.”
Researchers have been keen to develop nasal Covid vaccines since the earliest days of the pandemic because they are easier to administer than injections and have the potential to slash transmission by blocking the virus at the point of entry into the body. While existing vaccines are extremely good at preventing severe disease, they are far less effective at curbing the spread of the virus.
The AstraZeneca-funded phase 1 trial tested the efficacy of the Oxford vaccine when delivered through a simple device that sprays droplets up the nose. The trial involved 30 people who had not previously been vaccinated against Covid and 12 more who received the spray as a booster.
While the trial raised no safety issues, the researchers found that the spray produced “weak and inconsistent” immune responses, which, according to their report in eBioMedicine, were “insufficient to warrant further development of the current formulation/device combination”.
The scientists measured levels of both mucosal and systemic antibodies against Covid, found in the respiratory tract and bloodstream respectively. There was little evidence of mucosal antibodies after one nasal spray. After two doses, a handful of participants had mucosal antibodies, but the levels were only “rarely and modestly” above those seen after Covid infection.
Only a fraction of the trial volunteers had detectable systemic antibodies against Covid a month after one or two doses of the spray, and levels were typically lower than those seen after two jabs of the same vaccine.
The findings are particularly disappointing given China and India’s recent approval of two new nasal Covid vaccines. China’s Covid booster, developed by CanSino Biologics in Tianjin, is administered through a nebuliser that turns the liquid vaccine into a mist. India’s vaccine, developed by Bharat Biotech in Hyderabad, is a two-shot primary vaccination delivered via drops in the nose.
One possible problem with the Oxford spray is that the majority of the droplets may end up being swallowed and destroyed in the stomach rather than priming the immune system in the nose, throat and lungs. To get around this, the vaccine could be delivered at a higher concentration or reformulated so that more of the liquid sticks to the lining of the respiratory tract.
Prof Gordon Dougan, an expert in vaccinology, infection and genomics at the University of Cambridge, said that although the results were not promising, the data was “very helpful” for the field because nasal spray vaccines were so technically challenging. “We need better science to understand how to induce immunity through nasal and oral delivery,” he said. “It’s still not well understood.
“Nasal vaccines offer an opportunity to induce local immunity, potentially limiting transmission, which will be vital to prevent the emergence of vaccine escape variants.”