A novel mucosal vaccine delivery technology
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 neonatal Fc receptor (FcRn), which is expressed on mucosal epithelial cells, and transports both albumin and IgG across the mucosa. We have successfully engineered both albumin and IgG for improved binding to the receptor. Subunit vaccines can be genetically fused to WT or engineered variants of either albumin or the Fc portion of IgG.
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.
In this study, 168 BalbC mice and 885 transgenic mice will be used to test albumin- and Fc- based vaccine formulations, which are based on genetic fusion to hemagglutinin (HA) from influenza. Transgenic mice with the human form of FcRn will be used to test the human vaccine formulations as there are big cross-species differences in the FcRn-ligand binding relationships between human and mouse. Vaccines will be compared side-by-side for their ability to generate protective immune responses against H1 influenza. In addition, there will be investigated if albumin fused to HA from H7 influenza can elect protective immune responses against H7 influenza.
Intranasal delivery of the vaccine is gentle and will not cause any suffering. Influenza virus challenge after vaccination will cause influenza symptoms, and as a result of reduced appetite they will lose weight.
As there is not possible to mimic the human immune response in vitro,mice is the preferred choice of species to test the vaccine formulations as they have similarities to the human immune system. The smallest number of groups and mice in each group has been optimized to obtain significance.
Specifically, we take advantage of the neonatal Fc receptor (FcRn), which is expressed on mucosal epithelial cells, and transports both albumin and IgG across the mucosa. We have successfully engineered both albumin and IgG for improved binding to the receptor. Subunit vaccines can be genetically fused to WT or engineered variants of either albumin or the Fc portion of IgG.
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.
In this study, 168 BalbC mice and 885 transgenic mice will be used to test albumin- and Fc- based vaccine formulations, which are based on genetic fusion to hemagglutinin (HA) from influenza. Transgenic mice with the human form of FcRn will be used to test the human vaccine formulations as there are big cross-species differences in the FcRn-ligand binding relationships between human and mouse. Vaccines will be compared side-by-side for their ability to generate protective immune responses against H1 influenza. In addition, there will be investigated if albumin fused to HA from H7 influenza can elect protective immune responses against H7 influenza.
Intranasal delivery of the vaccine is gentle and will not cause any suffering. Influenza virus challenge after vaccination will cause influenza symptoms, and as a result of reduced appetite they will lose weight.
As there is not possible to mimic the human immune response in vitro,mice is the preferred choice of species to test the vaccine formulations as they have similarities to the human immune system. The smallest number of groups and mice in each group has been optimized to obtain significance.