Protective effects of STI-2020 antibody delivered post-infection by the intranasal or intravenous route in a Syrian golden hamster COVID-19 model

Yanwen Fu, Junki Maruyama, Alok Singh, Reyna Lim, Arthur Ledesma, Daniel Lee, Laura Rivero-Nava, Jamie Ko, Ianne Rivera, Rachel A. Sattler, John T. Manning, Lisa Kerwin, Heyue Zhou, Mark Brunswick, Damien Bresson, Henry Ji, Slobodan Paessler, Robert D. Allen

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Oct 29 2020

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Fingerprint Dive into the research topics of 'Protective effects of STI-2020 antibody delivered post-infection by the intranasal or intravenous route in a Syrian golden hamster COVID-19 model'. Together they form a unique fingerprint.

Cite this