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Principal Investigator: JAY A BERZOFSKY
Organization: DIVISION OF BASIC SCIENCES - NCI
Fiscal Year: 2020
Award: $512,699
Funding agency: National Cancer Institute
This project just began in April, 2020, during the COVID-19-induced closure of NIH labs, with very few people allowed to work, so it is very early ( 3 months) and progress is limited on each of the above sub-studies. In vitro studies in macaque bronchioalveolar lavage cells: So far, we have seen some effects in vitro on these cells of stimulating them with recombinant spike protein to affect expression of ACE2 and of interferons, that may play a role in infection. Little effect was seen on other cytokine or chemokine production. This work is in progress. In vivo vaccine studies in macaques: the animals have been primed IM with spike in different adjuvants and boosted systemically with spike in nanoparticles. Some T cell responses have been induced by the different regimens, and serum and BAL fluid for antibody responses have been collected and are being assayed. It is too soon to determine which regimen is more immunogenic. If we can arrange a challenge at a BSL3 facility that can handle the virus (being negotiated), we hope to challenge the animals with SARS-CoV-2 to measure vaccine efficacy and correlate that with different immune responses. In vivo studies in mice: ACE2-transgenic mice have been ordered but their shipment was delayed until the end of July. In wild type B6 mice, we have immunized with recombinant spike protein in several different adjuvants to determine the best formulation. That work is in progress. The DNA vaccine with spike protein coupled to a chemokine is being constructed and that work is in progress. Human cell lines: We have received the immortalized human lung epithelial cell lines, that express ACE2, from John Minna at UTSW, as well as some of his non-small-cell lung cancer cell lines that also express ACE2. We have just obtained (mid-July) an antibody to ACE2 that we will use to verify expression. These lines have now been thawed and are being grown up, but no results of planned studies to stimulate with spike protein have been obtained yet. We intend to measure production of chemokines, cytokines, and other factors that may affect the COVID-19 disease course, as noted above.
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