Intranasal vaccines are attractive as they offer an easier method of vaccination than intramuscular delivery. They don’t require a trained health professional to administer the vaccine (a vaccine would be packaged similar to many over-the-counter hay fever nasal sprays); while in offering an alternative for people who don’t like needles, they could boost vaccination rates.
But researchers looking at administering the AstraZeneca COVID-19 vaccine (ChAdOx1 nCoV-19) via intranasal format have found other advantages when it comes to effectiveness and transmission.
Vaccines are typically injected into muscle, producing antibodies that circulate in the blood but aren’t necessarily present in the nose and nasal passages. This means vaccinated individuals could still become infected and transmit the virus.
In contrast, an intranasal vaccine could target the virus at the point of entry into the body as well as in the bloodstream. With less virus in the nasal passages, that would decrease the risk that vaccinated people spread the virus.
And pre-clinical studies suggest an intranasal vaccine could be just as effective – if not more effective – in creating an immune response.
Pre-clinical trials
The US NIH’s National Institute of Allergy and Infectious Diseases (NIAID) tested intranasal delivery of the Oxford/AstraZeneca vaccine in hamsters and monkeys, with the results published in July in Science Translational Medicine.
The team first compared spraying the vaccine intranasally to intramuscular injection in hamsters. Both routes of administration produced high levels of antibodies against SARS-CoV-2 in the blood after a single dose. Levels of antibodies in blood were actually higher after intranasal administration.
Vaccinated hamsters and a group of unvaccinated animals were then exposed to SARS-CoV-2, either by direct administration into the nose or through contact with infected hamsters. Both routes of vaccine administration protected hamsters from serious disease. Unvaccinated hamsters lost weight and showed signs of lung damage, but vaccinated hamsters did not. The animals that received intranasal vaccination also had substantially less infectious virus in their nasal passages than unvaccinated animals.
Next, the scientists tested two doses of the intranasal vaccine in four monkeys. As in the hamsters, antibodies were found in the blood after the second dose, this time at levels similar to those seen in people who have recovered from COVID-19.
The monkeys were then exposed to SARS-CoV-2. Compared to four unvaccinated monkeys, those that received the intranasal vaccine had less virus in their noses and in lung tissue. Three of the unvaccinated animals tested developed symptoms of pneumonia, while none of the vaccinated monkeys did.
The pre-clinical studies involved a small sample size and the study's authors note that, although 'very encouraging', the results cannot be considered statistically signficant. Nevertheless, they merit further research, they say.
Clinical trials
Now, the University of Oxford is running a Phase 1 clinical trial: testing the intranasal vaccine in 54 healthy adults aged 18-55 years old.
The study is looking at the vaccine across five different groups. The first three groups will cover vaccine naïve individuals with either one or two doses. The doses will cover three different levels: a standard dose equivalent to that given by injection, plus two lower doses.
The fourth group will look at the intranasal vaccine as a booster for those who have already been vaccinated with the same vaccine via the typical intramuscular route; while the fifth group will investigate the booster in those who were initially vaccinated with Pfizer/BioNTech’s mRNA vaccine.
“The trial will give us valuable information on the safety of the vaccine and extent of the immune response when administered intranasally in healthy volunteers,” says the Jenner Institute, the vaccine development arm of the University of Oxford. “We do this by giving participants the vaccine via a nasal spray, in addition to doing blood tests, nasal swabs, and collecting information about any symptoms that occur after vaccination.”
The trial started in May and will last for 12 months.
