Five years ago, we fell into the first period of confinement linked to the Cavid-19 pandemic. Nine months later, the first doses of vaccine were available. These vaccines, with messenger RNA or non -replicative viral vector, were all presented in the form of an intramuscular injection. At the same time, researchers from the University of Tours and Inrae worked on the development of a vaccine in the form of a nasal spray. Today, they are about to test their nasal vaccine for the first time on humans.
This vaccine, like its predecessors, is administered intramuscularly. All lead to “systemic immunity”. This means that they activate immune cells, including lymphocytes, throughout the body. These cells then join the infected organs and tissues via blood circulation. The disadvantage of this process is that it does not conceive enough B and T lymphocytes in the nasal cavity and the lungs. However, the respiratory tract is the entry point of SARS-COV-2. This is where the body's defenses should be concentrated, to block the virus as soon as possible.
How would a nasal spray be more effective?
A respiratory virus infection always induces a mucous and systemic immune response. The first is characterized by the presence of immunoglobulins A (IGA). The second is characterized by the presence of immunoglobulins G (IGG). The IGA protect the upper respiratory tract, while the IGG mainly protect the lower respiratory tract.
The nasal vaccine induces a systemic and local immune response, blocking the virus as soon as it entered the body. Credits: LovalTech
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However, the vaccines that are administered by intramuscular or intradermal route mainly induce IGG, not IGA. Thus, currently available anti-Cavid vaccines are effective in protecting from the serious forms of the disease. On the other hand, their action is not sufficient to cause “sterilizing” immunity, which would imply that one is no longer carrying the virus (the immune response completely eliminating the organism virus).
This is the raison d'être of intranasal vaccination: induce a systemic, but also local immune response, at the point of entry of the virus. The activation of immune cells in the nasal mucosa – which constitute the first line of defense of our body – would guarantee rapid and efficient protection. They would eliminate the virus before it has time to spread and multiply in the respiratory system. This would stop the transmission chain.
An approach that has already proven itself
A group of researchers, led by Professor Isabelle Dimier-Poisson, worked on this project in 2020. The team was inspired by a process which it had previously implemented, to protect the Saimiris (small monkeys from South America) kept in captivity of toxoplasmosis. She had developed a vaccine in the form of nasal spray inducing a mucous and systemic immune response against the parasite Toxoplasma gondiiresponsible for the disease.
The first vaccination campaign, launched at the end of 2017 in five French pilot zoos, was a success. Since then, many monkeys and other sensitive species have benefited from this vaccination against toxoplasmosis.
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The intranasal anti-Cavid vaccine was first subject to pre-clinical tests, in the laboratory, then on hamsters, to demonstrate the effectiveness of the concept. Then, in 2022, the LovalTech company, a start-up specializing in Biotechnologies based in Tours, was born. His goal? Continue the industrial development of the nasal vaccine until its marketing. Thanks to public and private funding, the young shoot was able to accelerate the development of the vaccine and explore new vaccine applications.
After demonstrating the safety and efficiency of the animal vaccine candidate in recent years, LovalTech has obtained authorization from the National Medicines Safety Agency and the Persons Protection Committee to launch the first clinical trial on humans, baptized Mucoboost.
A “new generation” vaccination
The Messenger RNA Vaccine Cumirnaty JN.1 contains Brétovameran. It is a coding mRNA for the SARS-COV-2 SPIKE (s) (s) (of its variant Omicron JN.1 more precisely), encapsulated in lipid nanoparticles. This protein, located on the viral envelope, makes it possible to trigger an immune response. In the event of subsequent infection, immune cells recognize protein and neutralize viral particles.
However, experience has shown that protein S can mutate rapidly, potentially reducing the effectiveness of vaccines.
The experimental intranasal vaccine should ensure effective protection against all variants of the virus and block its transmission, thus reducing interhuman contagiousness and the circulation of the virus. But what exactly does it contain?
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Research on SARS type coronaviruses highlighted other characteristics of these viruses, in addition to the protein S. They notably identified nucleoprotein (N), which does not vary as viruses are evolving. The designers of the vaccine therefore integrated this protein into the formulation of their product, so that it remains effective vis-à-vis new variants.
The vaccine thus consists of a fusion protein (incorporating the S and N proteins), associated with a muco-excipient. The latter, specially developed by LovalTech, allows optimal delivery of vaccination proteins.
“” This innovation represents a strategic opportunity to rethink vaccination, improve immune coverage and face future world health challenges “Concludes Patrick Barillot, president and co-founder of Lovaltech.
A clinical trial to confirm the superiority of the intranasal approach
Phase I of the trial will start at the end of April, at the CHRU CHRU in Tours clinical investigation center, then, in June, at the Cochin-Pasteur clinical investigation center in Paris. Both belong to the I-Reivac network, dedicated to clinical research in vaccinology. This first phase aims to assess tolerance and immune response in healthy people, in order to determine the optimal dose that should be used for phase II.
Test officials will recruit 36 volunteers, aged 18 to 55. They will be divided into three groups of 12 people, each receiving another dosage of the vaccine. After the administration of the product, each participant will be invited to six follow -up visits, with organic samples. The preliminary results are expected in the fall of 2025.
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The second phase should be initiated in early 2026. It will aim to validate the superiority of the intranasal vaccine compared to an mRNA vaccine, to reduce the contagiousness of the COVVI-19. This phase will involve some 200 volunteers, followed in five centers in the I-Reivac network.
If the potential of this vaccine is confirmed, it will not only improve the protection against COVVI-19, but will also serve as a model to fight against other respiratory infections.
With an unwavering passion for local news, Christopher leads our editorial team with integrity and dedication. With over 20 years’ experience, he is the backbone of Wouldsayso, ensuring that we stay true to our mission to inform.
