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Principal Investigator: KIM HASENKRUG
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2020
Award: $72,116
Funding agency: National Institute of Allergy and Infectious Diseases
A primary goal of this project is to understand the basic immunological responses involved in the recovery from COVID-19 using animal models including mice, hamsters and non-human primates. To date we have completed the first phase of testing SARS-CoV-2-infected rhesus macaques that were depleted of CD4+ or CD8+ T cells or dually depleted of both subsets. 3 macaques in each of 4 groups including a control non-depleted group have been analyzed. Nasal, throat and rectal swabs along with blood and bronchoalveolar fluids were collected in a kinetic manner over a period of 6 weeks and the animals were then re-infected to analyze anamnestic immune responses. The animals were then studied for an additional 2 weeks and were euthanized for harvesting of tissues for immunohistochemical study. A second study of an additional 3 animals per group is now underway so that we can obtain groups sizes large enough to obtain statistically significant data for publication. Similar studies in the hamste model are in preparation. An IACUC-approved animal study proposal is in place, the regents have been obtained and hamsters have been ordered. In collaboration with Dr. Bosio we are also looking forward to testing a mouse model in a similar manner. Dr. Bosio is also collaborating with us to develop mouse models for testing the live attenuated vaccine once it is ready from Dr. Raul Andino at UCSF. Vaccine studies in aged mice are also underway in our laboratory with the goal of making elderly mice more reactive to vaccination and to develop stronger protective immunity. This is a collaboration with Dr. Irving Weissman at Stanford University who has developed a method to rejuvenate the immune systems of old mice, which, like humans, become less able to respond to new infections as they age, a phenomenon known as immune senescence. Finally, our project to develop aptamers that bind to SARS-CoV-2 spike protein receptor binding domain to block interactions with human ACE-2 and interfere with viral entry into host cells is at the stage of synthesizing likely candidates. Aptamers have undergone 11 rounds of selection and sequencing has revealed 30 candidates that will be tested for in vitro interference of virus entry.
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