Influenza - prophylaxis and therapy
The main aim for the present project is to assess the immunological signatures and protective efficacy of novel influenza vaccines, as well as selected therapeutic drugs.
Experimental overview: Briefly, the mice will be vaccinated or treated with the selected drug, and the formation of immune responses monitored. It is also important to investigate whether it can actually protect against influenza virus, so the mice will be infected with different strains of influenza to assess the protective capacities. For the most vulnerable groups (negative controls) we expect to see a weight loss associated with influenza infection, but the duration of this moderate discomfort should last only a few days prior to recovery or euthanization.
Benefit: Influenza viruses cause annual epidemics and occasional pandemics. Vaccination is the main method of prophylaxis, but today’s vaccines have an efficacy range of only 10-60%. (Please note that even with this low efficacy, they still save many lives on an annual basis.) Currently used influenza vaccines contain attenuated or inactivated virus particles, and are produced by growing viruses in chicken eggs. This production process is very time consuming, which means that each year scientists will make an educated guess as to which influenza strains should be included in next years’ vaccine. The guess is difficult, and vaccine efficacy is typically hampered by antigenic mismatches between the virus strains in the vaccine and the strains circulating in the population (which have mutated further). For efficient protection of the population, we thus need a next generation influenza vaccines. The present project on development of improved vaccine strategies is thus important. Further, the present SARS-CoV-2 pandemic has highlighted the need for efficient therapeutic drugs. Many of these target cellular properties of the host, rather than virus specific factors. The experiments here described use therapeutic drugs that may be important for future treatment of severe disease following infection with different viruses, but influenza is the model system used for now.
Animals: Here we apply for use of 2334 mice, and where different strains will be used to facilitate translation to larger animals and humans, as well as to validate results across different immunological phenotypes
Use of the 3Rs: Prior to vaccination, all vaccines and drugs will be validated in vitro for structural and functional integrity. Unfortunately, the complexity of immune formation prevents in vitro assessments of vaccine efficacy, necessitating animal experiments. Results from previous experiments have been used to design experiments with as few animals as possible, but still maintain statistical significance. Where possible, methods will be refined to reduce discomfort for the animals.
Experimental overview: Briefly, the mice will be vaccinated or treated with the selected drug, and the formation of immune responses monitored. It is also important to investigate whether it can actually protect against influenza virus, so the mice will be infected with different strains of influenza to assess the protective capacities. For the most vulnerable groups (negative controls) we expect to see a weight loss associated with influenza infection, but the duration of this moderate discomfort should last only a few days prior to recovery or euthanization.
Benefit: Influenza viruses cause annual epidemics and occasional pandemics. Vaccination is the main method of prophylaxis, but today’s vaccines have an efficacy range of only 10-60%. (Please note that even with this low efficacy, they still save many lives on an annual basis.) Currently used influenza vaccines contain attenuated or inactivated virus particles, and are produced by growing viruses in chicken eggs. This production process is very time consuming, which means that each year scientists will make an educated guess as to which influenza strains should be included in next years’ vaccine. The guess is difficult, and vaccine efficacy is typically hampered by antigenic mismatches between the virus strains in the vaccine and the strains circulating in the population (which have mutated further). For efficient protection of the population, we thus need a next generation influenza vaccines. The present project on development of improved vaccine strategies is thus important. Further, the present SARS-CoV-2 pandemic has highlighted the need for efficient therapeutic drugs. Many of these target cellular properties of the host, rather than virus specific factors. The experiments here described use therapeutic drugs that may be important for future treatment of severe disease following infection with different viruses, but influenza is the model system used for now.
Animals: Here we apply for use of 2334 mice, and where different strains will be used to facilitate translation to larger animals and humans, as well as to validate results across different immunological phenotypes
Use of the 3Rs: Prior to vaccination, all vaccines and drugs will be validated in vitro for structural and functional integrity. Unfortunately, the complexity of immune formation prevents in vitro assessments of vaccine efficacy, necessitating animal experiments. Results from previous experiments have been used to design experiments with as few animals as possible, but still maintain statistical significance. Where possible, methods will be refined to reduce discomfort for the animals.