Hopes of distributing the Oxford/AstraZeneca Covid vaccine as a nasal spray have been hit after researchers said it performed poorly in its first clinical trial.
The disappointing results 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 nebulizers capable of delivering drugs deep into lungs.
“The nasal spray did not perform as well in this study as we had hoped,” said Dr Sandy Douglas, lead researcher of the trial at the Jenner Institute in Oxford. “Delivering vaccines to the nose and lungs remains a promising approach, but this study suggests there will likely be challenges in making nasal sprays a reliable option.”
Researchers have been keen to develop nasal Covid vaccines since the early days of the pandemic because they are easier to administer than injections and have the potential to reduce transmission by blocking the virus at the point of entry into the body. While existing vaccines are extremely effective at preventing serious disease, they are much less effective at curbing the spread of the virus.
The AstraZeneca-funded Phase 1 trial tested the effectiveness of the Oxford vaccine when given via a simple device that sprays droplets into the nose. The trial involved 30 people who had not previously been vaccinated against Covid and 12 others who received the spray as a booster.
Although the trial did not raise any safety concerns, the researchers found that the spray produced “weak and inconsistent” immune responses, which their report in eBioMedicine said were “insufficient to warrant further development of the combination.” current wording/device”.
Scientists measured levels of mucosal and systemic antibodies against Covid, found in the respiratory tract and bloodstream, respectively. There was little evidence of mucosal antibodies after nasal spray. After two doses, a handful of participants had mucosal antibodies, but levels were only “rarely and modestly” higher than those seen after Covid infection.
Only a fraction of the volunteers in the trial had detectable systemic antibodies against Covid a month after one or two doses of the spray, and the levels were generally lower than those seen after two injections of the same vaccine.
The results are particularly disappointing given the recent approval by China and India of two new nasal vaccines against Covid. The Chinese Covid booster, developed by CanSino Biologics in Tianjin, is delivered through a nebulizer that turns the liquid vaccine into a mist. India’s vaccine, developed by Bharat Biotech in Hyderabad, is a two-shot primary vaccination given as drops in the nose.
A 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 circumvent this problem, the vaccine could be given at a higher concentration or reformulated so that more of the liquid adheres to the lining of the airways.
Professor Gordon Dougan, an expert in vaccinology, infection and genomics at the University of Cambridge, said that while the results were not promising, the data was “very useful” for the field because nasal spray vaccines were so technically difficult. “We need better science to understand how to induce immunity by nasal and oral administration,” he said. “It is not yet well understood.
“Nasal vaccines offer an opportunity to induce local, potentially transmission-limiting immunity that will be vital in preventing the emergence of vaccine escape variants.”