Identification of protective human monoclonal antibodies using a K18 hACE2 transgenic mouse SARS-CoV-2 challenge model
Borate, B.; Pino, P. A.; Hicks, A.; Garcia, J. I.; Garcia-Vilanova, A.; Ye, C.; Park, J.-G.; Maingot, B.; Rodriguez, O.; Saveria, T.; Holman, D.; Schendel, S. L.; Saphire, E. O.; Martinez-Sobrido, L.; Torrelles, J. B.; Fiore-Gartland, A.
Show abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), uses human angiotensin converting enzyme 2 (hACE2) as its obligate receptor for cell entry. The K18 hACE2 transgenic mouse line, which expresses hACE2 under control of the human keratin 18 (K18) promoter, is used as an animal model for the study of COVID-19 pathogenesis. Here, we evaluate this model in the screening of human monoclonal antibody (hmAb) therapies against SARS-CoV-2. We included 206 hmAbs from the Coronavirus Immunotherapeutic Consortium Database (CoVIC-DB) and identified many that protected against a lethal challenge with the virus. Our data showed that mouse weight change from day 5 onward highly correlated with survival. Many of the protective hmAb candidates we identified also showed strong viral neutralization and spike protein (SP) binding when measured in vitro; however, in many cases, in vitro assays failed to identify protective hmAbs, suggesting that the mouse model may capture characteristics of the hmAbs that other methods cannot. Our findings demonstrate the relevance of including in vivo models for the characterization of therapeutics against SARS-CoV-2, as these improve both accuracy and expediency in the screening process.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- AZD7442 demonstrates prophylactic and therapeutic efficacy in non-human primates and extended half-life in humans 95%
- SARS-CoV-2 Omicron neutralization by therapeutic antibodies, convalescent sera, and post-mRNA vaccine booster 94%
- Antibodies targeting Crimean-Congo hemorrhagic fever virus GP38 limit vascular leak and viral spread 93%
Similar papers in this journal
- Infants and young children generate more durable antibody responses to SARS-CoV-2 infection than adults 94%
- Immunogenicity and Protective Efficacy of an Intranasal Live-attenuated Vaccine Against SARS-CoV-2 in Preclinical Animal Models 93%
- BCG administration promotes the long-term protection afforded by a single-dose intranasal adenovirus-based SARS-CoV-2 vaccine 93%
Similar papers in this journal
- A Murine Model of Post-acute Neurological Sequelae Following SARS-CoV-2 Variant Infection 94%
- Egg-derived anti-SARS-CoV-2 immunoglobulin Y (IgY) with broad variant activity as intranasal prophylaxis against COVID-19: preclinical studies and randomized controlled phase 1 clinical trial 94%
- Novel Spike-stabilized trimers with improved production protect K18-hACE2 mice and golden Syrian hamsters from the highly pathogenic SARS-CoV-2 Beta variant. 93%
Similar papers in this journal
- Non-neutralizing SARS-CoV-2 N-terminal domain antibodies protect mice against severe disease using Fc-mediated effector functions 95%
- A combination of potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against the SARS-CoV-2 delta variant 94%
- mRNA induced expression of human angiotensin-converting enzyme 2 in mice for the study of the adaptive immune response to severe acute respiratory syndrome coronavirus 2 93%
Similar papers in this journal
- The effect of molnupiravir and nirmatrelvir on SARS-CoV-2 genome diversity in severe models of COVID-19. 93%
- Ronapreve (REGN-CoV; casirivimab and imdevimab) reduces the viral burden and alters the pulmonary response to the SARS-CoV 2 Delta variant (B.1.617.2) in K18-hACE2 mice using an experimental design reflective of a treatment use case 92%
- Monitoring SARS-CoV-2 infection using a double reporter-expressing virus 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.