Analysis: a successful nasal vaccine could change the way we deal with Covid-19, but there are huge challenges

By now we're all familiar with the Covid-19 vaccines that come as a couple of shots in the arm. They’ve proven highly effective at preventing severe illness, hospitalisation and deaths from the virus, but not at stopping the virus in its tracks.

"The one thing we haven't been able to do is block transmission. That wouldn't be unusual with lots of vaccines," says Professor of Immunology Christine Loscher, Associate Dean for Research at DCU. Which is why scientists have been looking in a different direction when it comes to controlling Covid-19: a nasal vaccine.

Putting the Covid-19 vaccine intramuscularly into the arm generates a systemic immune response, giving us lots of antibodies in the circulation, lots of killer T cells and memory T cells, Loscher explains. But the huge advantage of nasal vaccines is that they act directly in the local area where the virus enters the body; the nose and mouth.

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We actually have nine FDA approved nasal vaccines for different viruses, says Loscher. A "nasal" vaccine is either given orally, as a spray, or inhaled, for example through a nebuliser covering the nose and mouth. "The flu vaccine is the one that we'd be most familiar with. It's a small nasal spray up into the nose, predominantly given to children, for obvious reasons, because needles are harder for children, but also because their immune system is a little bit less mature and you get a really good response in the mucosal sites. We also have nasal vaccines for cholera and for polio. They're given orally, so you actually generate the immunity in the mucosal sites and the gut. The flu vaccine is actually one of the very few sprays."

When a vaccine is delivered into the mouth or the nose, it activates the local cells in the mucosal sites to be able to be "tissue-resident immune cells". "What that means, is that they are able to produce specific antibodies at the site of entry. That means then, that if Covid comes in, you get a much faster response, with these cells being able to produce antibody to stop [the virus] causing an infection."

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This gives nasal vaccines the potential to bring us what's called sterilising immunity. If we can block transmission, by stopping someone actually getting the infection, then we can get to a place where Covid-19 is minimised altogether, says Loscher. "We haven't been able to achieve that. Not because the vaccine's not working properly, but because Covid is so good at transmitting and because it's at such high levels in the community," says Loscher. The virus is essentially outpacing the vaccines.

"If you remember all the other stuff that we're vaccinated against, we're very rarely ever in contact with anyone who has all those infections. You're very rarely in contact with people who have measles or mumps or rubella or whooping cough, so the chances of us ever encountering those infections is actually really low. Whereas we’re bombarded with Covid all the time, so it's not surprising that [the Covid-19 vaccine] is not able to completely block it."

In October 2022, Oxford/AstraZeneca suffered a setback in their quest for a nasal vaccine. Their efforts were dealt a blow when the nasal spray "didn’t perform as well" as they had hoped in the Phase 1 clinical trial. It delivered "weak and inconsistent" immune responses and "mucosal antibody responses" were only found in a minority of the participants, the findings said.

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"There's about 100 nasal vaccines in development at the moment, that’s how important it is," says Loscher. China approved a nasal Covid-19 vaccine in September and Iran has administered 5 million doses of a nasal vaccine since October 2021, but we haven’t seen data from either of them, she adds.

Loscher explains that nasal vaccines present huge challenges. "One of the difficulties is, that when you give a nasal vaccine, particularly when you do a spray into the nose, it immediately goes down the back of the throat and is swallowed. Trying to get a nasal vaccine to be present for long enough at that site is a challenge. Maybe it needs to be stickier, so that it stays there longer and gets a chance to induce a good immune response."

"The other issue is that because you're reliant on the vaccine producing cells that can make local antibody, it's not as easy as just measuring an antibody in the bloodstream. Trying to measure the amount of local antibody and knowing how much you need of it to give protection is a real challenge."

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"So [nasal vaccine trials] are more difficult trials to run than they are for the [injection vaccine] where you're looking for systemic, circulating antibodies in the blood. Here, we are checking circulating antibodies, but that doesn't tell you the local antibody that's being produced at the mucosal site. Which is this 'IgA antibody,’ which is specifically for protection of these mucosal sites that you find at the back of your nose and your respiratory tract."

Because we already have very good vaccines against Covid-19, the ethics around running trials for other types of vaccines are harder to square, says Loscher. At this point it’s also difficult to find people who have never had Covid to take part in the trial.

AstraZeneca not working first time is probably going to give them a lot of information about what they need to do to get it to work better, says Loscher. "Lots of things fail before we get them right, so I wouldn't be discouraged by it. The concept of having a nasal vaccine to help get us out of this Covid cycle that we're in, is still a very positive one that we should pursue."


The views expressed here are those of the author and do not represent or reflect the views of RTÉ