In collaboration with co-Principal Investigators Dr. Gerry Wright (McMaster) and Dr. Mike Tyers (Université de Montreal), the Miller Laboratory secured funding in the CIHR’s first round of COVID-19 Rapid Response competition to find new drugs to treat SARS-CoV-2 infections, and to identify approved drugs that could be repurposed. These investigations have involved extensive high-throughput screening of compounds against both seasonal human coronaviruses in CL2 labs, as well as SARS-CoV-2 in McMaster’s CL3 laboratory. In parallel, dozens of genome-wide CRISPR screens have been performed to identify druggable genetic pathways required for CoV replication. These efforts have already yielded several promising leads for new and approved compounds that are undergoing extensive validation.
The Miller Laboratory has also pioneered several quantitative serological assays to measure the functions of antibodies that target influenza virus. The COVID-19 pandemic necessitated the development of new tools and reagents to both identify and evaluate the antibody responses of individuals who have been infected with SARS-CoV-2. To this end, the Miller team generated a series of critical reagents to aid in the characterization of the antibody response against SARS-CoV-2. These have been used to perform cross-sectional studies of SARS-CoV-2 immunity (https://pubmed.ncbi.nlm.nih.gov/33015650/)
in collaboration with Dr. Andres Finzi (Université de Montreal), and to aid in the development on on-site serological assays to identify individuals who have previously been infected (https://www.medrxiv.org/content/10.1101/2020.09.11.20192690v1) in collaboration with Dr. Dawn Bowdish and Dr. Ishac Nazy. The Miller team has also developed several functional assays to measure neutralizing antibodies and those capable of eliciting Fc-dependent effector functions against SARS-CoV-2. These are being deployed in several ongoing studies that were funded in the second round of CIHR COVID-19 Rapid Response grants, including a Hutterite cohort study in collaboration with Dr. Mark Loeb (McMaster), and a major international study of the PURE cohort in collaboration with Dr. Darryl Leong (McMaster).
The serological assays described above will also be extremely useful in evaluating the response to several SARS-CoV-2 vaccines under development by the Miller Laboratory and collaborators. These include yeast-based active and passive vaccine formulations funded by the Weston Family Microbiome Initiative (in collaboration with Dr. Mike Tyers (Université de Montreal), and an Adenovirus-vectored vaccine in collaboration with several investigators at MIRC, led by Drs. Zhou Xing and Brian Lichty.
We have also worked closely with the Mossman Laboratory to characterize molecular and immunological properties of SARS-CoV-2 (https://pubmed.ncbi.nlm.nih.gov/32902372/; https://pubmed.ncbi.nlm.nih.gov/32558639/).
Finally, in recognition of the important role played by industry in finding solutions to COVID-19, the Miller Team has been involved in several contracts to test novel decontamination solutions (including an NSERC Alliance project in collaboration with Dr. Marc Aucoin (University of Waterloo) and Trojan Technologies), and potential antiviral therapies. This is been a massive collective effort involving an extensive group of academic and industrial collaborators. The Miller Laboratory is especially grateful to McMaster’s Biosafety officers, Drs. Jennifer Robertson and Kristen Carrigan for the exceptional efforts they have made to ensure safe and efficient operations in the CL3 facility that have been essential to our ability to respond to this pandemic.