A novel mucosal vaccine delivery technology
1 Purpose
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.
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.
2 Distress
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 they will lose weight.
3 Expected benefit
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.
4 Number of animals, and what kind
A total number of 1528 hFcRn transgenic mice will be used. Most of them will also be transgenic for IgG1Fc.
100 FcRn KO mice will be used.
100 Balb/C mice will be used.
5 How to adhere to 3R
Highly qualified personnel will take care of the research animals, mice will have an enriched environment, and we will minimize stress by handing the animals gently and in a quiet surrounding. By a thorough characterization using biochemical and cellular methods, we have limited the number of albumin-vaccine candidates of interest to an absolute minimum. Nevertheless, in vivo models are necessary to evaluate the pharmacokinetics and immune responses of the developed vaccines, which depend on several factors that cannot be measured in vitro.
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.
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.
2 Distress
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 they will lose weight.
3 Expected benefit
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.
4 Number of animals, and what kind
A total number of 1528 hFcRn transgenic mice will be used. Most of them will also be transgenic for IgG1Fc.
100 FcRn KO mice will be used.
100 Balb/C mice will be used.
5 How to adhere to 3R
Highly qualified personnel will take care of the research animals, mice will have an enriched environment, and we will minimize stress by handing the animals gently and in a quiet surrounding. By a thorough characterization using biochemical and cellular methods, we have limited the number of albumin-vaccine candidates of interest to an absolute minimum. Nevertheless, in vivo models are necessary to evaluate the pharmacokinetics and immune responses of the developed vaccines, which depend on several factors that cannot be measured in vitro.