Imagine inhaling just a few drops of liquid or mist to protect yourself from COVID-19. That’s the idea behind nasal COVID-19 vaccines, and they’ve been attracting a lot of attention lately as a spray or liquid. These nasal vaccines would be based on the same technology as regular vaccines given by injection. But as Mayuresh Abhyankar, a University of Virginia researcher who studies infectious diseases and works on nasal vaccines, explains, there are many immunological benefits to vaccinating someone exactly where the coronavirus is likely to begin its attack.

1. What are nasal vaccines?

Nasal vaccines, as the name suggests, are administered through the nose. More specifically, called intranasal vaccines, these vaccines are liquids that can be administered as a spray or through a dropper or syringe. The most common nasal vaccine is FluMist, a nasal spray that uses inactivated flu viruses to protect against influenza. An intranasal vaccine could be an attenuated live virus similar to FluMist, a nucleic acid vaccine like mRNA coronavirus vaccines, or a protein vaccine like hepatitis B vaccines or the CorbeVax coronavirus vaccine.

Intranasal vaccines are best for protecting against pathogens that enter through the nose, such as the flu or the coronavirus. By mimicking the first step of natural exposure to an airborne pathogen, these vaccines help train a person’s immune system at the potential site of infection. Scientists have shown that the initial immune response in the airways after a person is exposed to an airborne virus can affect how sick a person gets. So, in theory, intranasal vaccines could offer better protection than vaccines given through an arm syringe.

2. How does the coronavirus infect people?

A cross section of a human, highlighting the respiratory system of the nose, throat and lungs.
Nasal vaccines differ from intramuscular vaccines in that they mimic the mechanism of infection and elicit a stronger immune response, specifically in the throat and nose.
7activestudio/iStock via Getty Images

SARS-CoV-2, the virus that causes COVID-19, normally enters the body through the nose and lands on the lining of the back of the nose and throat. The virus then enters the cells it touches, replicating and spreading.

Just below these cells of the mucosa are many types of immune cells that make up what is called the mucosal immune system. Cells of the mucosal immune system are the first to recognize invading coronavirus particles and mount a protective response.

In an unvaccinated person, it takes about two weeks for these immune cells to mount a protective response after encountering the coronavirus. By this time, the virus can easily have infected other parts of the body, such as the lungs, which can lead to serious illness.

Nasal vaccines follow many of the same steps. When you inhale a nasal vaccine, the particles land on the lining of your nasal cavity or throat, enter cells there, and trigger an immune response. This process teaches the body about the coronavirus and allows it to deal with future real infections.

3. How do nasal and intramuscular vaccines differ?

If you get a COVID-19 shot in your arm, the vaccine will trigger a powerful immune response in the cells near where you got the shot. It also causes your immune system to produce some coronavirus-specific antibodies and other immune cells elsewhere in your body.

When the coronavirus begins to infect cells in a person’s airways, nearby immune cells begin to mount a defense. Your body also sends antiviral immune cells and antibodies from other places to the site of infection. But by the time enough coronavirus-specific immune cells gather around the site of infection to stop the virus from replicating, the virus has likely already started to spread throughout the body, making it difficult for the immune system to keep up.

Nasal vaccines mimic the virus to prime the immune system for a virus like any other vaccine. But most importantly, they also mimic the infection process and enhance the protective response within the mucosal immune system of the nose and throat. Put simply, intranasal vaccinations are like knowing there’s going to be a burglary and getting your guards in the right spot before the trouble even starts.

Science confirms this idea. In a head-to-head comparison, AstraZeneca’s COVID-19 vaccine provided greater protection in hamsters vaccinated intranasally than in those vaccinated intramuscularly.

Nasal vaccination could also be used in conjunction with intramuscular immunization. In a recent study, my colleagues and I gave some mice both a nasal and an intramuscular vaccine and exposed them to a lethal dose of SARS-CoV-2 – 100% of these mixed vaccines survived compared to just 10% of the unvaccinated mice . We are now testing whether this mixed approach is superior to purely intranasal or purely intramuscular approaches alone.

Finally, intranasal vaccines are painless, non-invasive, and require no special training to use.

A nurse inserting an eyedropper into a woman's nose.
Nasal vaccines, like the liquid flu vaccine the nurse here gives a patient, are easier to administer and don’t require needles, but it can be more difficult to ensure the full dose is absorbed.
CDC/Douglas Jordan via Wikimedia Commons

4. What are the risks of nasal vaccines?

Finding the right dosage can be more difficult with nasal vaccines than with vaccination, especially in young children. If someone has a stuffy nose or sneezes out part of the vaccine before it is fully absorbed, this can result in a lower than desired dose.

There are also some unique health risks. All vaccines go through rigorous safety testing and clinical trials, but these processes are particularly important for nasal vaccines because the nose is close to the brain. In 2000, 27.7% of people who received inactivated intranasal influenza vaccination in Switzerland developed temporary facial paralysis – also known as Bell’s palsy. The researchers later found that a bacterial toxin added to the vaccine to boost the immune response was the culprit.

This is the only reported case of neurological problems attributed to intranasal vaccines, but it’s something to consider.

5. How long will it take for intranasal COVID-19 vaccines to be ready?

As of the end of May 2022, there are no approved intranasal COVID-19 vaccines for human use. Seven are currently in clinical trials, and three of those — manufactured by Beijing Wantai Biological Pharmacy, Bharat Biotech, and Codagenix and Serum Institute of India — are in Phase 3 human trials.

In the coming months, the results of these studies will show not only how safe these promising new vaccines are, but also whether they outperform the vaccines used today.

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