Nasal COVID-19 vaccines help prepare the body for infection where it begins – in your nose and throat

Imagine breathing in 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 have been getting a lot of attention lately as a spray or liquid. These nasal vaccines would be based on the same technology as normal vaccines administered by injection. but if Mayuresh Abhyankara University of Virginia researcher who studies infectious diseases and works on nasal vaccines explains that vaccinating someone where the coronavirus is likely to start its attack has many immunological benefits.

1. What Are Nasal Vaccines?

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

Intranasal vaccines are best suited to protect 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 first immune response in the respiratory tract after a person is exposed to an airborne virus can affect how sick a person gets† So in theory, intranasal vaccines could: provide better protection than vaccines given by injection into the arm.

2. How does the coronavirus infect people?

Nasal vaccines differ from intramuscular vaccines in that they mimic the infection mechanism and specifically trigger a stronger immune response in the throat and nose.
7activestudio/iStock via Getty Images

SARS-CoV-2, the virus that causes COVID-19, usually enters the body through the nose and ends up on the mucous membrane at the back of the nasal cavity and in the throat. The virus then enters the cells it touches, replicates and spreads.

Just below these cells of the mucosa are many types of immune cells called mucosal immune system† Cells of the mucosal immune system are the first to identify invading coronavirus particles and begin to mount a protective response.

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

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

3. How do nasal and intramuscular vaccines differ?

When you get a COVID-19 shot in your arm, the vaccine triggers a strong immune response in the cells near where you got the injection. It also causes your immune system to produce certain coronavirus-specific antibodies and other immune cells in other places in your body.

When the coronavirus begins to infect cells in a person’s respiratory tract, the nearby immune cells will begin to defend themselves. Your body will too send antiviral immune cells and antibodies from other locations 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 multiplying, the virus has likely already started spreading throughout the body, making it difficult for the immune system to keep up.

Nasal vaccines mimic the virus to preparing the immune system for a virus, just like any other vaccine. More importantly, they also mimic the infection process and the protective response within the mucosal immune system of nose and throat† In simple terms, intranasal vaccines are like knowing there will be a break-in and putting your guards in the right location before the problems even begin.

Science confirms this idea. In a direct comparison, AstraZeneca’s COVID-19 vaccine yielded better protection in hamsters vaccinated intranasally compared to those vaccinated intramuscularly.

Nasal vaccination can 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 vaccinated mice survived, compared to only 10% of unvaccinated mice. We are now testing whether this mixed approach is superior to intranasal-only or intramuscular-only approaches alone.

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

A nurse putting a dropper in a woman's nose.

Nasal vaccines, such as the liquid flu vaccine that the nurse gives a patient here, are easier to administer and require no needles, but may be more difficult to ensure that the full dose is absorbed.
CDC/Douglas Jordan via Wikimedia Commons

4. What are the risks of nasal vaccines?

Getting the right dose can be more difficult with nasal vaccines than an injection, especially in young children. If someone has a stuffy nose or sneezes out some of the vaccine before it’s fully absorbed, it could result in a lower than desired dose.

There are also some unique health risks. All vaccines undergo rigorous safety testing and clinical trials, but these processes are especially important for nasal vaccines due to the simple fact that the nose is close to the brain. In 2000, 27.7% of people in Switzerland received an inactivated intranasal flu vaccine developed transient facial paralysis – also known as Bell’s palsy. 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 due to intranasal vaccines, but it is 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. There are currently seven in clinical trialsand three of them – manufactured by Beijing Wantai Biological Pharmacy, Bharat Biotech and Codagenix and Serum Institute of India – are in phase 3 human trials

The results of these trials will show in the coming months not only how safe these promising new vaccines are, but also whether they outperform the vaccines in use now.

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