Our group has extensive experience in generating robust human immune systems from human fetal hematopoietic stem cells (HSCs) and thymus tissue in mice that lack immune systems of their own. These humanized mice are termed HIS mice. We have developed some novel permutations of the model that optimize immune function and health of the animals. We aim to further adapt these models for COVID-19 research by introducing the human ACE2 receptor, plus a class I HLA molecule, into the lung epithelium of mice that receive human HSCs and pig or human thymus tissue. We will further optimize this model by substituting alternatives to fetal human thymus tissue to make it eligible for federal funding, which is currently difficult to apply for if human fetal tissue is required.
The optimized model will be used for the following purposes:
1) To gain an understanding of the relative role of human immune responses vs direct effects of the virus on human lung tissue;
2) To test vaccination approaches;
3) To test new immunotherapies and anti-viral therapies in infected mice.
