AstraZeneca’s intranasally administered vaccine against COVID-19 did not work as expected in a small study published Tuesday, suggesting there are likely to be challenges in making nasal sprays a reliable option.
Findings from a Phase 1 clinical trial, published in the journal eBioMedicine, show that mucosal antibody responses were generated in a minority of participants.
Systemic immune responses, which involve many other immune cells, to intranasal vaccination were also weaker compared to intramuscular vaccination, the researchers said.
The study was conducted in collaboration with the University of Oxford and used the same ChAdOx1 adenovirus vector-based vaccine, which is already licensed for use by injection.
The ChAdOx1 vector used in the vaccine is a weakened version of a common cold virus (adenovirus) that has been genetically modified, making it impossible for it to replicate in humans.
The latest study is believed to be the first to publish data from the administration of an adenovirus-vectored vaccine using a simple nasal spray.
The trial enrolled 30 previously unvaccinated participants to receive a primary dose of the intranasal vaccine.
In addition, the researchers studied the feasibility of the intranasal vaccine as a booster. The intranasal vaccine was administered to 12 participants, who had previously received a standard schedule of two doses of COVID-19 vaccine by injection.
The study found that the vaccine did not elicit a consistent mucosal antibody or strong systemic immune response.
However, no serious adverse events or safety concerns were reported during the trial, the researchers said.
“The nasal spray did not work as well in this study as we had hoped,” said Associate Professor Sandy Douglas, principal investigator of the trial at the University of Oxford.
“This was quite different from recent data from China, which has suggested that good results can be achieved by delivering a similar vaccine deep into the lungs with a more complex nebulizer device,” Douglas said.
India last month granted emergency use approval for Hyderabad-based Bharat Biotech’s iNCOVACC, an intranasal antidote to the virus that its makers called “a global game changer.”
The company claimed the vaccine was “safe, well tolerated and immunogenic” compared to its own Covaxin in a phase III trial of more than 3,000 participants at 14 sites in India.
“A nasal spray vaccine similar to ours was recently approved for intranasal use in India and we look forward to peer-reviewed publication of the clinical trial data used to support that,” Douglas said.
“We believe that delivering 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,” he added.
One possibility, the researchers explained, is simply that most of the nasal spray vaccine ends up being swallowed and destroyed in the stomach; administration to the lungs could prevent this.
Another challenge is that researchers do not 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 that can block the transmission of respiratory pandemic viruses using delivery routes that are safe and practical on a large scale,” Douglas added.