Coronavirus Covid-19

Administered to the nasal mucosa, a spike-based formulation triggers rapid local defences that clear the COVID-19 virus where it enters.

In 2022, a year after Australia’s longest COVID-19 lockdowns, researchers from the Centenary Institute and the University of Sydney received a grant of almost $1 million from the NSW COVID-19 Vaccine Acceleration Research Grants Program to develop an intranasal COVID-19 vaccine.

Now, new research has been released by the team – finding that their formulation can stop infection in the nose before the virus spreads through the body, and to other people.

Dr Erica Stewart, Centenary Institute

Australian Pharmacist sat down with Dr Erica Stewart, first author and researcher at the Centenary Institute when the work was undertaken, to discuss how the vaccine works, its applications and why it could be the key to stopping the spread.

What is the vaccine’s mechanism of action?

By acting where the virus first enters, the nasal vaccine prompts a rapid, effective immune response that eliminates the virus, Dr Stewart said.

‘The adjuvant we used was Pam2Cys, a Toll-like receptor 2 (TLR2), and we showed that it was able to stimulate the immune response in the nasal passages,’ she said.

‘We formulated the SARS-CoV-2 spike protein with this adjuvant, which emulates bacteria to alert the immune system that there is a danger and it should respond.’

When administered as a booster after a standard injection, the treatment also provided additional protection to vital organs, including the lungs and brain – pointing to the benefits of focusing immune responses within the upper airways.

Why target the nasal mucosa?

The nasal passage is an increasingly promising site for vaccine adjuvant formulation, Dr Stewart said.

‘It’s becoming more and more clear that the nasal passage is a very different immune environment to an injection in the muscle.’

Internationally, there are some other pre-clinical models of mucosal vaccines. ‘But most of those mucosal vaccines are viral vectors because there aren’t a lot of vaccine adjuvants that have been found to be effective nasally, which is part of the novelty of this study,’ she said.

The team had previously looked at intranasal vaccination in mice, using a model where the vaccine entered both the lungs and the nose. 

‘However, the main takeaway from this research was, when [administering] a very small volume to just the nose, we still got a really strong immune response in the blood,’ she said. ‘We also looked into the nose itself, and we could see that the immune cells were retained for long periods in the nasal passages, where they will be able to respond to infection quickly.’

There’s hope that these vaccines can potentially prevent infection and transmission by building immune defences directly in the upper airways where the virus first takes hold – a frontier that traditional vaccines have yet to reach. 

‘We currently reduce disease severity really well, but we’re still trying to block transmission,’ Dr Stewart said. ‘That’s what nasal vaccines are aiming to address.’

Who would benefit most from a nasal COVID-19 vaccine?

Vulnerable populations who are more susceptible to severe disease, hospitalisations and death.

‘Sometimes you’ll hear people say, “COVID-19 is over” – but people are still dying of it, including the elderly, immunocompromised people and those with other comorbidities,’ Dr Stewart said. 

Similar to how younger, healthy patients are advised to get the flu vaccine to protect more vulnerable members of the community – this vaccine offers an additional layer of protection.

‘It would be the vulnerable people who are benefiting, but the vaccine would be for everyone to try to reduce the circulation of the virus in our community,’ she said.

How would the vaccine fit into the routine immunisation schedule?

With most people vaccinated against COVID-19 or exposed to the virus, the mucosal vaccines will likely be used as a booster.

‘In the mouse model, both the vaccine as a booster or as a primary vaccination induced nasal immunity,’ Dr Stewart said.

It’s assumed that the nasal vaccine will be used as an annual seasonal dose, similar to the flu vaccine or COVID-19 boosters for certain populations.

‘We do have some evidence that the vaccine can neutralise against other variants, but [we need to explore] how well it protects people and for how long, because that would indicate whether continuous boosters are needed,’ she said.

It’s also anticipated that the nasal vaccine will be self-administered.

‘There are studies looking into self-administration of nasal vaccines, which could really help with distribution and access to these vaccines in the community,’ she said.

This mode of administration could be particularly beneficial for those who are needlephobic, including children.

‘For people who cannot stand getting a needle, this is a less invasive method of vaccination,’ Dr Stewart said.

The researchers say that while more work is needed, the results show strong potential for nasal vaccines to complement existing COVID-19 vaccines and provide an extra layer of protection against the virus in the future.