Challenges and opportunities of a mucosal platform for nasal vaccination Current vaccines against ongoing and emerging diseases allow a certain level of protection notably against severe forms of diseases. However, their effectiveness remains limited in many aspects: effectiveness often reduced against strains or variants, weak effect on reducing transmission between individuals, duration of protection often shorter than natural infection. To overcome these shortcomings, mucosal vaccination represents the best solution for both scientists and politicians (WHO). Indeed, vaccine administration by mucosal route is the only one capable of inducing the local immune system response, capable of blocking pathogens as soon as they enter. By stopping their dissemination in the body, this makes it possible to limit carriage and contagiousness, and in doing so, it reduces the risk of appearance of new variants. Thus, the race for mucosal vaccination, particularly respiratory, has accelerated sharply following the Covid-19 pandemic and represents a major challenge in terms of health on a worldwide scale. However, mucosal vaccination is a challenge where the transition from preclinical to clinical is often strewn with pitfalls and disappointments. Several key factors are obstacles to the success of vaccination by the mucosal route, namely obtaining a protective vaccine against even symptomatic forms of the disease, blocking inter-individual transmission (contagiousness) and finally maintaining this efficacy against multiple strains or variant of the same virus. Our research team (BioMAP laboratory, Joint University-INRAE ISP 1282 research unit), led by Professor Isabelle Dimier-Poisson, has recognized experience in immunology and mucosal vaccination. Based on our expertise, we have worked on an innovative mucosal vaccine platform strategy, carried by our start-up LoValTech, in order to deal with its multiple specificities. Our vaccine first vaccine candidate, anti-Covid-19 is based on three innovations: - The antigen: target of the virus, it represent the heart of the vaccine. It is an original fusion protein, designed in our laboratory, composed of the now famous Spike (S) protein associated with another protein of the virus, the Nucleoprotein (N). This fusion strategy allows our vaccine to maintain its efficacy against different variants since it targets some conserved parts of the virus, whatever the [variations of the S protein](https://theconversation.com/how-new-Covid-19-variants-emerge-natural-selection-and-the-evolution-of-sars-cov-2-176030). - To optimize the activation of the mucosal immune response, our antigen is wrapped in "nano-carriers". These nano-carriers are solely composed of sugar polymeric molecules, able to confer original properties of adhesion to the mucous membrane allowing an optimal administration of our protein. In this manner there is no need for adjuvant (likely to create inflammation), thus reducing the risk of side effects. - Finally, the last key element, a dedicated delivery system, or spray, capable of effectively depositing our vaccine in the nasal cavity, precisely at the level of the areas containing the mucosal immune cells.