A novel targeted mucosal vaccine

Almost all infections are initiated at mucosal surfaces, such as the respiratory tract, and therefore it is important that vaccines work so as to give immunity at the mucosal surfaces, as well as in the blood. However, vaccines are usually given intramuscularly or subcutaneously, and often do not give good protection at the actual site of infection. This research project aims to solve this problem. We have designed vaccine formulations of albumin fused to antigen. They are cost effective and easy to store and transport because they are very stable molecules. Furthermore, simple intranasal delivery makes the use of needles unnecessary. The vaccines are targeted to the neonatal Fc receptor expressed on mucosal surfaces that transports the vaccines into the body. We have a large panel of variants available, which bind strongly to the receptor, and excellent preclinical model systems for testing. We have shown very good immune responses against influenza virus proteins both in the blood and on mucous membranes of mice, and mice that are vaccinated are protected against subsequent viral challenge that kills unvaccinated mice.

Almost all infections are initiated at mucosal surfaces, such as the respiratory tract. There is a close association between mucosal epithelial cells and immune effector cells within the laminar propria, and this suggests that delivery of vaccines through mucosal surface is an ideal approach to achieve mucosal as well as systemic immunity. Yet, vaccines are usually given intramuscularly or subcutaneously, and often do not provide good protection at the actual site of infection. This research project aims to solve this problem by targeting vaccines to a receptor specific mechanism that delivers vaccines to the immune system via the intranasal mucosa. We have studied the structure and function of the receptor, and recently published a model for its interact ion with albumin. Furthermore, based on this work, we have identified albumin variants with greatly increased affinity for the receptor. In short, we plan to genetically fuse antigens to engineered albumin variants, and perform intranasal vaccination in w ild type and transgenic mice. Albumin is an extremely stable molecule and easy to produce in large amounts in recombinant form. Thus, we expect the vaccine formulation to be cost effective and easy to store and transport. Furthermore, simple intranasal de livery will make the use of needles unnecessary, which will decrease the risk for infections. This is a new strategy for mucosal vaccine delivery. As such, the project has high risk. However, as we have a large panel of albumin variants available, and exc ellent preclinical model systems for testing, we feel the objectives are realistic. If the strategy succeeds, the knowledge will be used to guide the design of a larger set of vaccines, which will greatly benefit health in low income countries.