Intranasal delivery of AstraZeneca COVID-19 vaccine fails to generate strong immune response
The study used the same adenovirus vector vaccine which is already licensed for use by injection. The trial enrolled 30 previously unvaccinated participants to receive a primary dose of the intranasal vaccine (some with one dose and some with two); as well as 12 participants who received it as a booster dose following a standard primary injection schedule.
Oxford University researchers found that antigen-specific mucosal antibody responses to intranasal vaccination were detectable in a minority of participants, rarely exceeding levels seen after SARS-CoV-2 infection. Systemic responses to intranasal vaccination were typically weaker than after intramuscular vaccination with ChAdOx1 nCoV-19.
Advantages of a simple nasal spray
Funded by AstraZeneca, the new Oxford study is believed to be the first to have published data from administration of an adenovirus-vectored vaccine using a simple nasal spray.
As well as the advantages of needle-free administration, this nasal spray offered a more practical option for large-scale vaccine campaigns than a more complex nebuliser device – such as that used by a COVID-19 vaccine recently licensed in China – say the researchers.
Researchers are encouraged, however, by the acceptable safety profile of the vaccine: and believe their findings, alongside other licensed or candidate vaccines, can help build up a body of knowledge.
‘The nasal spray did not perform as well in this study as we had hoped,” said Associate Professor Sandy Douglas, Chief Investigator of the trial at the Jenner Institute, University of Oxford.
CanSinoBio's 'Convidecia Air' Recombinant COVID-19 vaccine (adenovirus Type 5 vector) for inhalation was approved in China in September as a booster dose.
The vaccine uses the same platform as the intramuscular version Convidecia, using a nebulizer to change liquid into an aerosol for inhalation through the mouth.
Studies published in The Lancet indicated that Convidecia Air can induce strong humoral, cellular and mucosal immunity.
In September, Bharat Biotech received approval for emergency use in India for its COVID-19 nasal vaccine. iNCOVACC was developed using technology licensed from Washington University in St. Louis. The Phase 3 trial involved around 3,100 previously unvaccinated people and 875 people in a booster trial.
“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."
Possibilities for the future delivery of nasal vaccines could include formulations tailor-made for nasal spray use: such as higher concentrations or substances designed to help the vaccine stick in the nose instead of being swallowed.
“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," said Douglas.