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Animal Model Prescreening: Pre-exposure to SARS-CoV-2 impacts responses in the NHP model

Ricks, K. M.; Herbert, A. S.; Koehler, J. W.; Kuehnert, P. A.; Clements, T. L.; Shoemaker, C. J.; Kuehne, A. I.; O'Brien, C. M.; Coyne, S. R.; Delp, K. L.; Akers, K. S.; Dye, J. M.; Hooper, J. W.; Smith, J. M.; Kugelman, J. R.; Beitzel, B. F.; Gibson, K. M.; Johnston, S. C.; Minogue, T. D.

2020-07-06 immunology
10.1101/2020.07.06.189803 bioRxiv
Show abstract

COVID-19 presents herculean challenges to research and scientific communities for producing diagnostic and treatment solutions. Any return to normalcy requires rapid development of countermeasures, with animal models serving as a critical tool in testing vaccines and therapeutics. Animal disease status and potential COVID-19 exposure prior to study execution may severely bias efficacy testing. We developed a toolbox of immunological and molecular tests to monitor countermeasure impact on disease outcome and evaluate pre-challenge COVID-19 status. Assay application showed critical necessity for animal pre-screening. Specifically, real-time PCR results documented pre-exposure of an African Green Monkey prior to SARS-CoV-2 challenge with sequence confirmation as a community-acquired exposure. Longitudinal monitoring of nasopharyngeal swabs and serum showed pre-exposure impacted both viral disease course and resulting immunological response. This study demonstrates utility in a comprehensive pre-screening strategy for animal models, which captured the first documented case of community-acquired, non-human primate infection. One Sentence SummaryPre-exposure to SARS-CoV-2 affects biomarker responses in animal models, highlighting a need for robust pre-screening protocols prior to medical countermeasure studies.

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