Since the beginning of the corona pandemic, researchers have been working on mucosal vaccines that are administered through the nose. Now Berlin scientists, including researchers from the Charité – Universitätsmedizin Berlin, have developed and tested a live, weakened nasal vaccination. In the current issue of the journal Nature Microbiology*, the interdisciplinary team describes the special immune protection it triggers.

Berlin research team develops nasal vaccine against SARS-CoV-2

Coronaviruses spread primarily through the air. When an infected person speaks, coughs, sneezes or laughs, they excrete droplets containing viruses in their breath. This means that the pathogens can get into other people's respiratory tract and infect them. A Berlin research team wants to fight the virus exactly where it attacks first: on the mucous membranes of the nose, mouth, throat and lungs. For this purpose, the scientists have developed a nasally administered, live, attenuated vaccine against SARS-CoV-2 and were able to show how this provides even better immunity compared to conventional vaccines.

Last autumn, two preparations for nasal vaccination were approved in India and China. They are based on weakened adenoviruses, i.e. viruses that cause, among other things, respiratory or gastrointestinal diseases, but no longer reproduce themselves or only reproduce poorly and therefore do not cause any disease. Additional live nasal vaccines are being developed and tested worldwide.

Protects where the infection begins and beyond

The benefits of a vaccine in the form of a nasal spray go far beyond allowing people who are afraid of a shot to breathe a sigh of relief. When a vaccine is injected, immunity builds up primarily in the blood and throughout the body. However, this means that in an emergency, the immune system only detects and fights coronaviruses relatively late - because they penetrate the body through the mucous membranes of the upper respiratory tract. “This is exactly where we need local immunity if we want to intercept a respiratory virus at an early stage,” says co-last author of the study Dr. Jakob Trimpert, working group leader at the Institute for Virology at the Free University of Berlin.

“Nasal vaccines do this much better than vaccines that are injected and only reach the mucous membranes with difficulty or not at all,” says Dr. Emanuel Wyler, also co-final author. Since the outbreak of the pandemic, he has been researching the coronavirus in the RNA biology and post-transcriptional regulation working group led by Prof. Dr. Markus Landthaler at the Berlin Institute for Medical Systems Biology of the Max Delbrück Center (BIMSB-MDC).

Ideally, a live nasal vaccine stimulates the formation of antibodies, immunoglobulins A (IgA), directly on site and thus prevents infection from occurring in the first place. IgA is the most abundant immunoglobulin in the mucous membranes of the respiratory tract. It has the ability to neutralize pathogens by binding to them, preventing them from infecting respiratory cells. At the same time, the vaccination also stimulates systemic immune reactions, which overall contributes to effective protection against infection.

“Similar to antibodies in the mucous membrane, T memory cells located in the lung tissue are also useful. These white blood cells can remember pathogens and remain in the respective tissue after an infection. Their positioning in the lungs allows them to respond quickly to pathogens that invade through the respiratory tract,” says Dr. Geraldine Nouailles, immunologist and working group leader at the Clinic for Pulmonology, Respiratory Medicine and Intensive Care Medicine at the Charité. The co-first author refers to an observation that the team was able to make as part of the study: “We were able to demonstrate that previous intranasal vaccination also leads to increased reactivation of these local memory cells in the event of a SARS-CoV-2 infection. Of course we were particularly happy about that.”

Local immunity prevents viral infection

the effect of the newly developed nasal COVID-19 vaccine on hamster models that Dr. Trimpert and his team had already established themselves at the Free University of Berlin at the beginning of the pandemic. The animals are currently the most important non-transgenic model organism for COVID-19 , as they become infected with the same virus variants as humans and develop similar disease symptoms. After the vaccine was administered twice, the virus was no longer able to multiply in the model organism. “The immune memory was stimulated very well, and the mucous membranes were very well protected due to the high antibody concentration,” states Dr. Trims. The transmissibility of the virus could also be significantly reduced in this way.

In addition, the scientists compared the effectiveness of the live, attenuated vaccine with that of intramuscularly injected vaccines. To do this, they vaccinated the hamsters either twice with the live vaccine, once with an mRNA and then with the live vaccine, or twice with an mRNA or adenovirus-based vaccine. Using tissue samples from the nasal mucosa and lungs, they checked how strongly the viruses could still attack the mucous membrane cells SARS-CoV-2 They also determined the extent of the inflammatory response using single cell sequencing.

“The attenuated live vaccine performed better in all parameters than the comparison vaccines,” summarizes Dr. Wyler together. The decisive factor for this is probably that the nasally administered vaccine builds up immunity directly at the entry point of the virus. In addition, the live vaccine contains all virus components and not just the spike protein, as is the case with the mRNA vaccine. Although Spike is the most important antigen of the virus, the immune system can also recognize the virus using around 20 other proteins.

Protects better than conventional vaccines

The best protection against SARS coronavirus 2 was achieved by a double vaccination via the nose, followed by the combination of an injection of the mRNA vaccine into the muscle and the live vaccine then administered nasally. “This could make the live vaccine particularly interesting as a booster,” says co-first author of the study, Julia Adler, a veterinarian and doctoral student at the Institute of Virology at the Free University of Berlin.

The principle of live, weakened vaccines is old and is used, for example, in measles or rubella vaccinations. Previously, however, scientists created the attenuation randomly, sometimes by waiting years for mutations that produced a weakened virus. The Berlin researchers, on the other hand, have specifically changed the genetic code of the coronaviruses. “In this way, we want to prevent the weakened viruses from mutating back into a more aggressive variant,” explains Dr. Dusan Kunec, scientist at the Institute of Virology at the Free University of Berlin and also co-final author. The key co-developer of the vaccine emphasizes: “Our live vaccine is therefore safe and can be tailored to new virus variants.”

Next up are safety tests: The researchers are working with RocketVax AG, a Swiss start-up based in Basel. The biotech company is further developing the live-attenuated vaccine against SARS-CoV-2 and is preparing a clinical phase 1 study in humans. “We are very pleased to be playing a pioneering role in the development and production of the live attenuated SARS-CoV-2 vaccine in the form of a nasal spray. Our goal is to quickly scale production and advance clinical testing for market access to provide everyone with protection from COVID symptoms. We see great potential for seasonal nasal vaccines in the market,” says Dr. Vladimir Cmiljanovic, CEO of RocketVax.

Only time will tell which nasal vaccination ultimately provides the best protection. The manufacturers of the intranasal adenovirus vaccines developed in India and China have not yet applied for approval in Europe. However, according to the researchers, one thing is certain: Since they are administered as nasal sprays or drops, nasal vaccines are generally well suited for use with limited access to trained medical staff. They are also inexpensive to produce and easy to store and transport. Last but not least, live vaccines such as the one used here have been shown to provide cross-protection against related virus strains.

Source:

Charité

Already read? Are organic foods healthier than conventionally grown foods?


If you enjoyed this post and value the importance of well-founded information, become part of the exclusive Mimikama Club! Support our work and help us promote awareness and combat misinformation. As a club member you receive:

📬 Special Weekly Newsletter: Get exclusive content straight to your inbox.
🎥 Exclusive video* “Fact Checker Basic Course”: Learn from Andre Wolf how to recognize and combat misinformation.
📅 Early access to in-depth articles and fact checks: always be one step ahead.
📄 Bonus articles, just for you: Discover content you won't find anywhere else.
📝 Participation in webinars and workshops : Join us live or watch the recordings.
✔️ Quality exchange: Discuss safely in our comment function without trolls and bots.

Join us and become part of a community that stands for truth and clarity. Together we can make the world a little better!

* In this special course, Andre Wolf will teach you how to recognize and effectively combat misinformation. After completing the video, you have the opportunity to join our research team and actively participate in the education - an opportunity that is exclusively reserved for our club members!


Notes:
1) This content reflects the current state of affairs at the time of publication. The reproduction of individual images, screenshots, embeds or video sequences serves to discuss the topic. 2) Individual contributions were created through the use of machine assistance and were carefully checked by the Mimikama editorial team before publication. ( Reason )