Immunogenicity and protective efficacy of next generation influenza vaccines
The objective of this project is to assess immune responses, immunological memory and protective efficacy of next generation influenza vaccination. We will compare different novel influenza vaccines with the overall aim to increase cross-reactive immune responses against multiple influenza subtypes. We will investigate different vaccine candidates with and without adjuvants and the vaccines will mainly target the two main surface proteins of the influenza virus, hemagglutinin and neuraminidase.
There are currently no other alternatives to animals that can simulate the complexity of the immune responses required for protection in humans, thus it is necessary to perform experiments in animals. Our application is for 600 mice (BALB/c and CB6F1) over a 3 year period. We will perform dose response studies and test various prime-boost schedules to identify optimal dosing and immunisation schedule. The vaccines will be administered through the subcutaneous, intramuscular, sublingual and intranasal route, which will cause little discomfort to the animals. Blood will be sampled maximum once per week, in accordance with the guidelines. Ultimately, protective immunity will be assessed by viral influenza challenge. It will be essential to assess and compare the level of protection against influenza infection generated by the different vaccines and the complexity of an animal model cannot be replicated by in vitro methods, although intensive work is ongoing to create 3D immune cultures. Therefore, the mice will be infected with different influenza viruses to measure the level of homologous and heterologous protection against infection. We expect little adverse effects in the mice from our previous experience, however, weight loss is associated with influenza infection. The mice will be euthanised if the weight loss exceeds 20%. This is a humane endpoint and will prevent severe pain and discomfort for the animals. Dose titrations of influenza viruses will be carried out before the main experiments to identify the lethal dose for each virus. We also wish to use the viral challenge method to assess the level of protection provided by sera from humans that have received influenza vaccinations. The human sera will be injected intraperitoneally or intravenously through the tail vein (using volumes within the recommended limit) and the mice will be infected with influenza virus to show proof of concept protection
There are currently no other alternatives to animals that can simulate the complexity of the immune responses required for protection in humans, thus it is necessary to perform experiments in animals. Our application is for 600 mice (BALB/c and CB6F1) over a 3 year period. We will perform dose response studies and test various prime-boost schedules to identify optimal dosing and immunisation schedule. The vaccines will be administered through the subcutaneous, intramuscular, sublingual and intranasal route, which will cause little discomfort to the animals. Blood will be sampled maximum once per week, in accordance with the guidelines. Ultimately, protective immunity will be assessed by viral influenza challenge. It will be essential to assess and compare the level of protection against influenza infection generated by the different vaccines and the complexity of an animal model cannot be replicated by in vitro methods, although intensive work is ongoing to create 3D immune cultures. Therefore, the mice will be infected with different influenza viruses to measure the level of homologous and heterologous protection against infection. We expect little adverse effects in the mice from our previous experience, however, weight loss is associated with influenza infection. The mice will be euthanised if the weight loss exceeds 20%. This is a humane endpoint and will prevent severe pain and discomfort for the animals. Dose titrations of influenza viruses will be carried out before the main experiments to identify the lethal dose for each virus. We also wish to use the viral challenge method to assess the level of protection provided by sera from humans that have received influenza vaccinations. The human sera will be injected intraperitoneally or intravenously through the tail vein (using volumes within the recommended limit) and the mice will be infected with influenza virus to show proof of concept protection