Since the COVID-19 outbreak, scientists have been exploring the progression of mucosal vaccines that can be administered nasally. Recently, researchers in Berlin effectively created an attenuated nose vaccine. In a recent study, they detail the unique immune reaction it provokes.
The spread of coronavirus occurs primarily through the air when other inflamed people expel droplets of saliva containing the virus by talking, coughing, sneezing, or laughing. These airborne pathogens are then inhaled by others, resulting in infection. COVID-19 reasons, a study team in Berlin to target the initial entry point, the mucous membranes of the nose, mouth, throat and lungs.
Already in the fall of last year, two nasal vaccine formulations were approved for use in India and China. These are modified adenoviruses, which cause respiratory or gastrointestinal diseases, which disappear on their own, meaning they reflect poorly or prevent replication altogether and therefore never cause disease. Other live nasal vaccines are being developed and tested around the world lately.
After double vaccination with live attenuated vaccine (A), the hamster-style nasal mucosa is very well and has virtually no adjustments compared to SARS-CoV-2 (B). The mixture of live vaccines and mRNA (C) is also very effective, however, the virus still discovers small attack sites (stained brown) in the nasal mucosa (D). In comparison, double intramuscular vaccines are much less effective in terms of protecting the nasal mucosa (E F and G H). They allow the virus to damage the upper layers of tissue. Credit: Anne Voß, Institute of Veterinary Pathology, Freie Universität Berlin
The benefits of a nasal vaccine go far beyond offering an option for others who are afraid of desires. When a vaccine is injected, it induces immunity basically in the blood and body. However, this means that the immune formula does not stumble. Activate and fight coronaviruses until an infection has been relatively delayed, as they enter the frame through the mucous membranes of the upper respiratory tract. “So this is where we want local immunity if we want to intercept a respiratory virus early on,” says co-writer Dr. Jakob Trimpert, veterinarian and study organization leader at the Institute of Virology at Freie Universität. Berlin.
“Nasal vaccines are much more effective in this regard than injected vaccines, which fail or have difficulty reaching mucous membranes,” says Dr. Emanuel Wyler, co-senior author. He has been reading COVID-19 since the beginning of the pandemic at the Laboratory of RNA Biology and Post-Transcriptional Regulation, led by Professor Markus Landthaler at the Berlin Institute for Medical Systems Biology of the Max Delbrück Center (MDC-BIMSB).
In an ideal scenario, a live intranasal vaccine stimulates the formation of immunoglobulin A (IgA) antibodies directly at the site, preventing infection in the first place. IgA is the maximum immunoglobulin not unusual in the mucous membranes of the respiratory tract. It is to neutralize pathogens by binding to them and preventing them from infecting cells in the respiratory tract. At the same time, the vaccine stimulates systemic immune responses that help provide effective overall coverage against infection.
“Memory T cells that live in lung tissue play a similar role to antibodies in the mucosa,” explains Dr. Brown. Géraldine Nouailles, immunologist and leader of the study organization at the Department of Respirology, Respiratory Medicine and Intensive Care Medicine of Charité. Blood cells remain in the affected tissues long after an infection has passed and don’t forget about the pathogens they’ve encountered before. Thanks to their location in the lungs, they can temporarily react to viruses entering the respiratory tract. The co-author draws attention to one of the observations made by the team of his study: “We were able to show that previous intranasal vaccination leads to greater reactivation of those local memory cells in the next SARS-CoV-2 infection. Needless to say, we are satisfied with this result.
Scientists tested the effectiveness of the newly developed COVID-19 intranasal vaccine on hamster styles that Trimpert and his team established at Freie Universität Berlin at the beginning of the pandemic. These rodents are lately the most vital non-GMO-style organisms for new coronavirus research, as they can become inflamed with the same variants of the virus as humans and develop similar symptoms. They found that after two doses of the vaccine, the virus may no longer be reflected in the body of the style. “We observed strong activation of immunological memory and mucous membranes exceeded the maximum concentration of antibodies very well,” says Trimpert. The vaccine, therefore, could also particularly reduce the transmissibility of the virus.
In addition, the scientists compared the efficacy of the live attenuated vaccine with that of vaccines injected into muscle. To do this, they vaccinated the hamsters twice with the live vaccine, once with the mRNA and once with the live vaccine, or twice with an mRNA or adenovirus-based vaccine. Then, after the hamsters became inflamed with SARS-CoV-2, they used tissue samples from the nasal mucosa and lungs to see how well the virus could still attack mucosal cells. They also decided the extent of the inflammatory reaction using single cell sequencing. “The live attenuated vaccine performed better than the other vaccines in all parameters”, summarizes Wyler. This is probably greatest because the nasally administered vaccine boosts immunity directly at the site of virus entry. Furthermore, the live vaccine comprises all parts of the virus, not just the spike protein, as is the case with mRNA vaccines. Although the spike is in fact the major vital antigen of the virus, the immune formula can also recognize the virus from around 20 other proteins. Better than traditional vaccines
The most productive coverage against SARS-CoV-2 was provided through dual nasal vaccination, followed by the combination of muscle injection of the mRNA vaccine and the following nasal management of the live attenuated vaccine. attractive as reinforcement,” says exam co-author Julia Adler, a veterinarian and PhD student at the Institute of Virology at Freie Universität Berlin.
The precept of live attenuated vaccines is old and is already used in measles and rubella vaccines, for example. But in the past, scientists generated attenuation through possibility, through years of waiting for mutations that produced an attenuated virus to evolve. The Berlin researchers, on the other hand, were able to modify in particular the genetic code of coronaviruses. “We sought to prevent attenuated viruses from mutating again into a more competitive variant,” says Dr. Dusan Kunec, a scientist at the Institute of Virology. at Freie Universität Berlin and some other co-last writer of the studio. “This makes our live vaccine absolutely safe and means it can adapt to new virus variants,” says Kunec, who was instrumental in the vaccine’s progression.
The next step is safety testing: the researchers are involved with RocketVax AG, a Swiss start-up founded in Basel. humans. ” We are excited to be at the forefront of the progression and manufacture of the SARS-CoV-2 live attenuated nasal spray vaccine at RocketVax. Our purpose is to increase production and advance clinical progression towards market access to supply coverage opposite post-COVID symptoms for all. We see a wonderful outlook in the seasonal nasal vaccine market,” says Dr. Vladimir Cmiljanovic, CEO of RocketVax.
Time will tell which nasal vaccine will ultimately offer the most protection. Manufacturers of nasal adenovirus vaccines developed in India and China have not yet implemented their approval in Europe. But one thing is transparent to scientists: since they are administered as nasal sprays. Or drops, nasal vaccines are a smart choice for use in places where access to a trained medical corps of workers is limited. They are also affordable to produce and easy to buy and transport. Finally, live attenuated vaccines like this have been shown to offer cross-protection against similar virus strains and therefore probably also against long-term variants of SARS-CoV-2.
Reference: “The live attenuated vaccine sCPD9 causes an impressive systemic and mucosal immunity to SARS-CoV-2 variants in hamsters” through Geraldine Nouailles, Julia M. Adler, Peter Pennitz, Stefan Peidli, Luiz Gustavo Teixeira Alves, Morris Baumgardt, Judith Bushe, Anne Voss, Alina Langenhagen, Christine Langner, Ricardo Martin Vidal, Fabian Pott, Julia Kazmierski, Aileen Ebenig, Mona V. Lange, Michael D. Mühlebach, Cengiz Goekeri, Szandor Simmons, Na Xing, Azza Abdelgawad, Susanne Herwig, Günter Cichon, Daniela Niemeyer, Christian Drosten, Christine Goffinet, Markus Landthaler, Nils Blüthgen, Haibo Wu, Martin Witzenrath, Achim D. Gruber, Samantha D. Praktiknjo, Nikolaus Osterrieder, Emanuel Wyler, Dusan Kunec and Jakob Trimpert, April 3, 2023, Nature Microbiology . DOI: 10. 1038/s41564-023-01352-8
The study was funded by the German Research Foundation (DFG). Berlin-based researchers are engaging with Swiss company RocketVax AG in further development of the vaccine.
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