ArticleEBioMedicine2025
A humanised ACE2, TMPRSS2, and FCGRT mouse model reveals the protective efficacy of anti-receptor binding domain antibodies elicited by SARS-CoV-2 hybrid immunity.
Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- A biosafe mouse model for SARS-CoV-2 infection that more realistically simulates COVID-19 symptoms.Signal transduction and targeted therapy · 2026Article
- Current Advances and Applications of Animal Models in SARS-CoV-2 Pathogenesis and Vaccine Development.Microorganisms · 2025Review
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20 authors.
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Abstract
backgroundDespite the importance of vaccination- and infection-elicited antibodies (Abs) to SARS-CoV-2 immunity, current mouse models do not fully capture the dynamics of Ab-mediated immunity in vivo, including potential contributions of the neonatal Fc receptor, encoded by FCGRT.
methodsWe generated triple knock-in (TKI) mice expressing human ACE2, TMPRSS2, and FCGRT; and evaluated the protective efficacy of anti-SARS-CoV-2 monoclonal Abs (mAbs) and plasma from individuals with immunity elicited by vaccination alone plus SARS-CoV-2 infection-induced (hybrid) immunity.
findingsA human anti-SARS-CoV-2 mAb harbouring a half-life-extending mutation, but not the wild-type mAb, exhibited prolonged half-life in TKI mice and protected against lung infection with Omicron BA.2, validating the utility of these mice for evaluating therapeutic Abs. Pooled plasma from individuals with hybrid immunity to Delta, but not from vaccinated-only individuals, cleared infectious Delta from the lungs of TKI mice (P < 0.01), even though the two plasma pools had similar Delta-binding and -neutralising Ab titres in vitro. Similarly, plasma from individuals with hybrid Omicron BA.1/2 immunity, but not hybrid Delta immunity, decreased lung infection (P < 0.05) with BA.5 in TKI mice, despite the plasma pools having comparable BA.5-binding and -neutralising titres in vitro. Depletion of receptor-binding domain-targeting Abs from hybrid immune plasma abrogated their protection against infection.
interpretationThese results demonstrate the utility of TKI mice as a tool for the development of anti-SARS-CoV-2 mAb therapeutics, show that in vitro neutralisation assays do not accurately predict in vivo protection, and highlight the importance of hybrid immunity for eliciting protective anti-receptor-binding domain Abs.
fundingThis work was funded by grants from the e-Asia Joint Research Program (N10A650706 and N10A660577 to MLM, in collaboration with SS); the NIH (U19 AI142790-02S1 to EOS and SS and R44 AI157900 to KJ); the GHR Foundation (to SS and EOS); the Overton family (to SS and EOS); the Arvin Gottlieb Foundation (to SS and EOS), the Prebys Foundation (to SS); and the American Association of Immunologists Fellowship Program for Career Reentry (to FASB).
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