Testing a cancer patient-specific SARS-CoV-2 vaccine in chemotherapy- and radiation-treated pediatric brain tumor mouse models

NIH Pandemic-Era Grants

Pandemic Era Grants

2020

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Principal Investigator: JAMES M OLSON
Organization: FRED HUTCHINSON CANCER RESEARCH CENTER
Fiscal Year: 2020
Award: $176,000
Funding agency: National Cancer Institute

We are proposing work that will address the fundamental question of whether or not the SARS-CoV-2 Spike protein, the basis of many leading COVID19 vaccine approaches, is sufficiently antigenic to elicit neutralizing antibody responses in pediatric patients undergoing chemotherapy. We will immunize control mice and mice undergoing relevant regimens of chemotherapy with a SARS-CoV-2 Spike protein construct found in many leading vaccine approaches, as well as a SARS-CoV-2 Spike protein stabilized with a novel trimeric computationally designed circular tandem repeat protein (a ‘cTRP’ or ‘toroid’). We believe that the toroid scaffold will better stabilize the trimeric Spike protein in the ideal prefusion confirmation necessary for eliciting neutralizing antibody responses, as well as provide a necessary boost of immunogenicity through the in-silico sequence and repetitive nature of the cTRP scaffold. We will assess the antigenicity of the two constructs by examining the ability of serum isolated from the immunized cohort to neutralize a SARS-CoV-2 pseudo virus in a well-established infectivity assay. The results will inform the likelihood of vaccine effectiveness in patients undergoing chemotherapy and potentially provide an alternative vaccine candidate specifically designed to safely elicit antibody mediated protection in the immunocompromised.

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