Injecting a COVID-19, influenza, or tuberculosis vaccine under the skin doesn’t actually make much sense when you look closely. Pathogens enter through the nose or mouth with the air breathed into the upper respiratory tract and subsequently into the lungs. The vaccine injected under the skin is initially not effective where the infection occurs and needs to be averted. However, this type of systemic vaccination has worked since 1796, when Edward Jenner vaccinated the first human against smallpox. But for respiratory diseases, another vaccination method might work better.
Immune formation at the site of infection
Crucially, vaccines injected under the skin evoke a general immune response, but have little access to immune cells waiting for pathogens in the lining of the airways. But it is these cells that are responsible for fighting viruses and bacteria that we breathe. The strategy that numerous researchers around the world are pursuing is to let immune training take place where infection will later occur. They are developing intranasal vaccines that are sprayed on the nasal mucosa as a nasal spray. Astra Zeneca’s Fluenz Tetra has practically come a first live attenuated intranasal vaccine, but it only works well in children and is only used up to the age of 18.
This setback in the broad effect for people of all ages – research has been going on for decades on intranasal flu vaccines, which can be widely used and would be very useful, especially in areas with weak medical infrastructure – has resulted in vaccine research to a different strategy: aerosol vaccines that are inhaled as an allergy or asthma spray. For measles, tuberculosis and COVID-19, the first inhaled vaccines are already being tested on humans in the first clinical trials. For tuberculosis vaccines, direct comparisons have shown that inhaled vaccines make the mucous membranes of the airways suitable for attack by Mycobacterium tuberculosis – injections do not.
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Researchers at McMaster University in Canada have taken a closer look at what happens when a vaccine is inhaled and how it differs from an intranasal vaccine. They used a tuberculosis vaccine and measured droplet distribution, immune response, and efficacy in the mice. The Background: The only COVID-19 vaccine in a clinical study that can be inhaled also comes from the Canadian university. It is currently in Phase 1, the first level of human testing, and is designed as a booster dose after two or three doses of injected mRNA vaccines.
Vaccine nasal sprays only reach the upper respiratory tract
The McMaster team noted that vaccine nasal sprays primarily reach the nose and throat. In these upper respiratory tract areas, however, infections are rarely serious. Only when viruses penetrate deeper into the lungs do people get seriously ill, but intranasal vaccines cannot reach the deeper airways and therefore cannot even protect them.
Aerosol sprays, on the other hand, push the droplets containing the vaccine deep into the lungs. The researchers observed that significantly stronger immune responses to the vaccine take place there than in the upper respiratory tract.
To decide whether inhaled vaccines are superior to intranasal vaccines for tuberculosis vaccine alone or in general and future research should focus on them, they want to study the responses of the different mucous membranes of the nose and lungs to vaccines. They are looking for answers to questions about how well these mucous membranes can absorb vaccines, how strong the vaccination-triggered T-cell immunity is, and what long-term protection it offers.