Targeted nucleic acid vaccination to protect against infectious diseases
1. Formål:
The purpose of this project is to test the delivery of Vaccibody containing antigens from various infectious diseases as nucleic acids formulated in lipid nanoparticles (LNPs) in mice and evaluate the immune response. The LNPs are delivered intramuscularly and requires no electroporation. With this, we may compare the immune response generated by this novel way of delivering Vaccibody with previous results obtained by traditional delivery of Vaccibody as DNA with electroporation.
2. Skadevirkninger
Low - moderate burdens for the animals are expected from these experiments. The animals are sedated (sevoflurane or Zoletil-mix) under the procedures. The animals may only experience potential fright/discomfort may only be in conjunction with blood samples from the saphenous vain. It is not expected that the animals will experience any significant weakening of health or their condition in general.
3. Forventet nytteverdi
Nykode Therapeutics ASA is a Norwegian biotech company that has developed an unique DNA vaccine technology that may be used for both therapeutic and prophylactic vaccine purposes against infectious diseases. Through pre-clinical experiments, Vaccibody will gain scientific data to aid the preparation of applications to implement clinical trials with vaccines against infectious diseases.
4. Antal dyr og art
In these experiments, various doses of LNPs are injected intramuscularly (no electroporation is needed), and the specific immuneresponse the various antigens may give in the mice will be monitored at different time points and with various methods including serum ELISA, ELISpot and neutralizing antibody assays..For this work we will require 240 BALB/c mice, 60 C57BL/6 mice and 60 HLA-A2 mice, in total 360 mice.
5. Hvordan etterleve 3R
To reduce the number of animals in experiment, the Vaccibody nucleic acid constructs are tested and quality controlled in vitro to assess binding and folding of the vaccine proteins. Only the most promising constructs will proceed to animal experiments. The immune system consists of a complex network of cells and organs that cannot be imitated in vitro, and the specific immune response that the different antigens may elicit can only be tested in vivo. The animal welfare in these experiments are well cared for and all procedures (except blood samples from leg vain, and potential intramuscular injection) will happen under anesthesia. Human end points include:
Weight loss: Not more than 10%. General signs of disease or discomfort like brittle fur, strained respiration, humpback, reduced food intake, wounds, lack of grooming or reduced activity may be reasons for euthanasia, although the weight loss is not >10%.
The purpose of this project is to test the delivery of Vaccibody containing antigens from various infectious diseases as nucleic acids formulated in lipid nanoparticles (LNPs) in mice and evaluate the immune response. The LNPs are delivered intramuscularly and requires no electroporation. With this, we may compare the immune response generated by this novel way of delivering Vaccibody with previous results obtained by traditional delivery of Vaccibody as DNA with electroporation.
2. Skadevirkninger
Low - moderate burdens for the animals are expected from these experiments. The animals are sedated (sevoflurane or Zoletil-mix) under the procedures. The animals may only experience potential fright/discomfort may only be in conjunction with blood samples from the saphenous vain. It is not expected that the animals will experience any significant weakening of health or their condition in general.
3. Forventet nytteverdi
Nykode Therapeutics ASA is a Norwegian biotech company that has developed an unique DNA vaccine technology that may be used for both therapeutic and prophylactic vaccine purposes against infectious diseases. Through pre-clinical experiments, Vaccibody will gain scientific data to aid the preparation of applications to implement clinical trials with vaccines against infectious diseases.
4. Antal dyr og art
In these experiments, various doses of LNPs are injected intramuscularly (no electroporation is needed), and the specific immuneresponse the various antigens may give in the mice will be monitored at different time points and with various methods including serum ELISA, ELISpot and neutralizing antibody assays..For this work we will require 240 BALB/c mice, 60 C57BL/6 mice and 60 HLA-A2 mice, in total 360 mice.
5. Hvordan etterleve 3R
To reduce the number of animals in experiment, the Vaccibody nucleic acid constructs are tested and quality controlled in vitro to assess binding and folding of the vaccine proteins. Only the most promising constructs will proceed to animal experiments. The immune system consists of a complex network of cells and organs that cannot be imitated in vitro, and the specific immune response that the different antigens may elicit can only be tested in vivo. The animal welfare in these experiments are well cared for and all procedures (except blood samples from leg vain, and potential intramuscular injection) will happen under anesthesia. Human end points include:
Weight loss: Not more than 10%. General signs of disease or discomfort like brittle fur, strained respiration, humpback, reduced food intake, wounds, lack of grooming or reduced activity may be reasons for euthanasia, although the weight loss is not >10%.