Evaluation of Monoclonal Antibody Efficacy in K18-hACE2 Mice

Animal studies were carried out in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocols were approved by the Institutional Animal Care and Use Committee at the Washington University School of Medicine (assurance number A3381–01). Virus inoculations were performed under anesthesia that was induced and maintained with ketamine hydrochloride and xylazine, and all efforts were made to minimize animal suffering.
Heterozygous K18-hACE2 C57BL/6J mice (strain: 2B6.Cg-Tg(K18-ACE2)2Prlmn/J, Cat # 34860) were obtained from The Jackson Laboratory. Animals were housed in groups and fed standard chow diets.
Eight-week-old female K18-hACE2 C57BL/6 mice were administered 100 μg of 2130-1-0114-112, parental 2130, or isotype control anti-West Nile virus hE16 mAb^{61 (link)} by intraperitoneal injection one day before intranasal inoculation with 104 focus-forming units (FFU) of WA1/2020 D614G, BA.1.1 or BA.5. Animals were euthanized at 4 days post-infection and tissues were harvested for virological analysis.

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Desautels T.A., Arrildt K.T., Zemla A.T., Lau E.Y., Zhu F., Ricci D., Cronin S., Zost S.J., Binshtein E., Scheaffer S.M., Dadonaite B., Petersen B.K., Engdahl T.B., Chen E., Handal L.S., Hall L., Goforth J.W., Vashchenko D., Nguyen S., Weilhammer D.R., Lo J.K., Rubinfeld B., Saada E.A., Weisenberger T., Lee T.H., Whitener B., Case J.B., Ladd A., Silva M.S., Haluska R.M., Grzesiak E.A., Earnhart C.G., Hopkins S., Bates T.W., Thackray L.B., Segelke B.W., Lillo A.M., Sundaram S., Bloom J., Diamond M.S., Crowe JE J.r., Carnahan R.H, & Faissol D.M. (2023). Computationally restoring the potency of a clinical antibody against SARS-CoV-2 Omicron subvariants. bioRxiv.

Publication Preprint 2023

K18-hACE2 C57BL/6J mice K18-ACE2)2Prlmn/J,

Ace2 Anesthesia Animals C57bl mice Diets Female Heterozygous Infection Inoculation Institutional animal care and use committee Intraperitoneal injection Isotype Ketamine hydrochloride Laboratory animals Parental Strain Tissues Virus inoculations West nile virus Xylazine

Corresponding Organization : Lawrence Livermore National Laboratory

Other organizations : Lawrence Livermore National Security, Washington University in St. Louis, Los Alamos National Laboratory, Vanderbilt University Medical Center

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Variable analysis

independent variables

Administration of 100 μg of 2130-1-0114-112, parental 2130, or isotype control anti-West Nile virus hE16 mAb by intraperitoneal injection one day before intranasal inoculation

dependent variables

Virological analysis of tissues harvested at 4 days post-infection

control variables

Eight-week-old female K18-hACE2 C57BL/6 mice
Intranasal inoculation with 104 focus-forming units (FFU) of WA1/2020 D614G, BA.1.1 or BA.5
Housed in groups and fed standard chow diets

controls

Isotype control anti-West Nile virus hE16 mAb

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