Optimalisering: A novel mucosal vaccine delivery technology

Although today's vaccines save millions of lives every year, there is still a great need for completely new vaccine concepts that can provide significantly improved protection against infectious diseases. Infections occur mostly on our mucosal barriers where there is a close cooperation between the mucosal cell layers and underlying immune cells. The challenge, however, is that the vast majority of today's vaccines are given by injection, intramuscularly or subcutaneously. This does not necessarily give protective immunity at the mucosal barriers, where the infection actually occurs. Due to this, there is a great need for new strategies where the vaccine can be given via the mucosal surfaces in a needle-free manner, but so far, it has not succeeded in developing a method that is effective enough. In this project, the goal has been to solve this major challenge by developing a vaccine concept that can be directed to a receptor expressed at the mucosal surfaces for efficient delivery to underlying immune cells. We have now done this by utilizing unique molecular competence and tools. The concept may pave the way for a whole new generation of vaccines that can be given through the mucosal barriers and completely without the use of syringes. By molecular design, we have designed expression vectors that encode albumin and Fc-based subunit vaccines with different abilities to bind a receptor that is expressed by the mucosal epithelial cells. A production system has been established for pre-clinical testing where the purified proteins are intact and bind with favorable kinetics to the receptor. Influenza was chosen as the model system, which is clinically relevant. Thorough the studies, we have taken advantage of humanized mice, which is adapted to the biology in question. The vaccine is delivered via the nose and enter the lungs followed by binding to the receptor for subsequent delivery to underlying immune cells. The experiments show that the developed concept provides protective antibody responses, both at the site of infection and systematically. T cell responses are also obtained. The specific immune responses protect against a 5-times lethal dose of influenza. The effect is more robust for albumin and Fc variants that have been designed based on technologies patented throughout the project period. In particular, the albumin concept provides very robust responses that allow us to lower the dose 10 times and still achieve protection. We also show that the protective immunity persists over time. Last year, we were awarded a SPARK innovation project that is linked to this particular project, where the goal is to compare the mucosal delivery strategy with intradermal delivery with the aim to develop a broadly protective vaccine. As part of this, we have attracted a mentor from Pfizer with broad expertise in vaccines. The project personnel has participated in international conferences, also together with the project manager at TTO to learn how to translate research results into commercialization. Due to our very promising pre-clinical data, we are now in a phase where we have initial dialogue with partners, and where establishment of a company is discussed. We will actively seek funding for commercialization of the vaccine concept.

Prosjekter har bidratt til å skolere prosjektets deltagere i aktiviteter knyttet til innovasjonsløp og kommersialisering. De har deltatt på kurs i Norge og utlandet for å lære om hvordan man omsetter forskningsresultater til kommersialisering. Det har vært utstrakt samarbeid med TTO hvor deltagerne har fått erfaring med konfidensialitet, patentering og interaksjon med industripartnere. Dette er verdifull kunnskap som forskningsgruppen og miljøet for øvrig har dratt stor nytte av. Prosjektet har gitt oss et utvidet nasjonalt og globalt nettverk knyttet til vaksineutvikling, både akademisk og med industri. Resultatene som er oppnådd vil kunne bare vei for nye vaksinestrategier med store implikasjoner. Det vurderes også etablering av et norsk biotek-selskap.

Despite the fact that current vaccines save millions of lives each year, there remains an urgent medical need for new and more efficient vaccines. Strategies to combat serious outbreaks of viral infectious diseases are particularly important. Such infections are initiated at mucosal surfaces, where there is a close association between mucosal epithelial cells and immune effector cells. However, vaccines are usually given intramuscularly or subcutaneously, and often do not provide sufficient protection at the site of infection. Therefore, significant efforts have been initiated by biotech companies and academic groups to explore vaccine delivery through mucosal surfaces. However, mucosal tissues form barriers that prevent direct delivery. We aim to solve the problem by targeting subunit vaccines to a receptor-specific pathway for delivery across mucosa. Specifically, we take advantage of the receptor FcRn, which is expressed on mucosal endothelial cells, and transports both albumin and IgG across mucosa. We have successfully engineered both albumin and IgG for improved binding to the receptor. Subunit vaccines can be genetically fused to either engineered albumin or the engineered Fc portion of IgG. Preliminary data show efficient transcellular transport. Furthermore, we observed a robust immune response after mucosal delivery of an albumin-antigen fusion, and complete protection against influenza A in a mouse model. Our technology makes the use of syringes and needles unnecessary, which is very convenient and decreases the risk for infections by blood borne pathogens due to needle reuse. Furthermore, albumin is an extremely stable protein which is easy to produce recombinantly, and as such, we expect albumin fusions to be cost effective as well as easy to store and transport. The concept is novel and described in a recently filed patent application. If successful, this project will prepare the ground for establishment of a new biotech company in Norway.