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bioRxiv · 10.1101/2020.10.28.359836

Protective Effects of STI-2020 Antibody Delivered Post-Infection by the Intranasal or Intravenous Route in a Syrian Golden Hamster COVID-19 Model

Fu, Y.·Maruyama, J.·Singh, A.·Lim, R.·Ledesma, A.·Lee, D.·Rivero-Nava, L.·Ko, J.·Rivera, I.·Sattler, R. A.·Manning, J. T.·Kerwin, L.·Zhou, H.·Brunswick, M.·Bresson, D.·Ji, H.·Paessler, S.·Allen, R. D.
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Abstract

We have previously reported that the SARS-CoV-2 neutralizing antibody, STI-2020, potently inhibits cytopathic effects of infection by genetically diverse clinical SARS-CoV-2 pandemic isolates in vitro, and has demonstrated efficacy in a hamster model of COVID-19 when administered by the intravenous route immediately following infection. We now have extended our in vivo studies of STI-2020 to include disease treatment efficacy, profiling of biodistribution of STI-2020 in mice when antibody is delivered intranasally (IN) or intravenously (IV), as well as pharmacokinetics in mice following IN antibody administration. Importantly, SARS-CoV-2-infected hamsters were treated with STI-2020 using these routes, and treatment effects on severity and duration of COVID-19-like disease in this model were evaluated. In SARS-CoV-2 infected hamsters, treatment with STI-2020 12 hours post-infection using the IN route led to a decrease in severity of clinical disease signs and a more robust recovery during 9 days of infection as compared to animals treated with an isotype control antibody. Treatment via the IV route using the same dose and timing regimen resulted in a decrease in the average number of consecutive days that infected animals experienced weight loss, shortening the duration of disease and allowing recovery to begin more rapidly in STI-2020 treated animals. Following IN administration in mice, STI-2020 was detected within 10 minutes in both lung tissue and lung lavage. The half-life of STI-2020 in lung tissue is approximately 25 hours. We are currently investigating the minimum effective dose of IN-delivered STI-2020 in the hamster model as well as establishing the relative benefit of delivering neutralizing antibodies by both IV and IN routes.

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Fu, Y., Maruyama, J., Singh, A., Lim, R., Ledesma, A., Lee, D., Rivero-Nava, L., Ko, J., Rivera, I., Sattler, R. A., Manning, J. T., Kerwin, L., Zhou, H., Brunswick, M., Bresson, D., Ji, H., Paessler, S., Allen, R. D.. 2020-10-29. Protective Effects of STI-2020 Antibody Delivered Post-Infection by the Intranasal or Intravenous Route in a Syrian Golden Hamster COVID-19 Model. https://doi.org/10.1101/2020.10.28.359836

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