In fact, injecting a COVID-19 vaccine, the flu, or tuberculosis under the skin doesn’t make much sense when you look closely. Pathogens penetrate the nose or mouth with breathed air into the upper respiratory tract and later into the lungs. The vaccine given under the skin is not initially effective where the infection to be averted is taking place. However, this type of systemic vaccination has been in place since 1796, when Edward Jenner vaccinated the first person against smallpox. But for respiratory diseases, another method of vaccination could work better.
Immune training at the site of infection
The bottom line is that vaccines given under the skin elicit an overall immune response, but have poor access to immune cells that are waiting for pathogens in the lining of the airways. But it is these cells that are responsible for fighting the viruses and bacteria we breathe. The strategy followed by many researchers around the world is to let immune training take place where the infection later occurs. They develop intranasal vaccines that are sprayed on the nasal mucosa as a nasal spray. With Flustra Tetra from Astra Zeneca, the first intranasal attenuated live vaccine came into practice – but it only works well in children and is only used under the age of 18.
This failure in a widespread effect on people of all ages – research into intranasal influenza vaccines that can be widely used and would be very useful, especially in areas with poor medical infrastructure – has been going on for decades – has led vaccine research to a different strategy: aerosol vaccines that are inhaled as a spray for allergies or asthma. The first inhaled measles, tuberculosis and COVID-19 vaccines are already being tested in humans in early clinical trials. For tuberculosis vaccines, direct comparisons have shown that inhaled vaccines make the mucous membranes of the airways suitable for infecting Mycobacterium tuberculosis – not injections.
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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 mice. Background: The only COVID-19 vaccine in a clinical study that can be inhaled is also from a Canadian university. It is currently in Phase 1, the first level of human testing, and is proposed 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 observed that the nasal spray sprays primarily reached the nose and throat. However, infections are rarely severe in these upper respiratory tract. Only when the viruses penetrate deeper into the lungs do people become seriously ill – but intranasal vaccines do not enter the deeper airways and therefore cannot even protect them.
Aerosol sprays, on the other hand, drive vaccine-containing droplets deep into the lungs. The researchers observed that there were significantly stronger immune responses to the vaccine than in the upper respiratory tract.
In order to decide whether inhaled vaccines are better than intranasal vaccines for tuberculosis vaccine alone or in general, and future research should focus on them, they want to study the responses of different mucous membranes in the nose and lungs to vaccines. They are looking for answers to the questions of how well these mucous membranes can absorb vaccines, how strong the T-cell immunity elicited by vaccination is, and what long-term protection it offers.