An update on the anti-spike monoclonal antibody pipeline for SARS-CoV-2

Focosi, Daniele; Franchini, Massimo; Casadevall, Arturo; Maggi, Fabrizio

doi:10.1016/j.cmi.2024.04.012

Clinical Microbiology and Infection

2024

DOI: 10.1016/j.cmi.2024.04.012

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An update on the anti-spike monoclonal antibody pipeline for SARS-CoV-2

Daniele Focosi,

Massimo Franchini,

Arturo Casadevall

et al.

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2024

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Cited by 3 publications

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Considerations for the development of monoclonal antibodies to address new viral variants in COVID-19

Casadevall,

McConnell,

Focosi

2024

Expert Opinion on Biological Therapy

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Considerations for the development of monoclonal antibodies to address new viral variants in COVID-19

Casadevall,

McConnell,

Focosi

2024

Expert Opinion on Biological Therapy

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Escape of SARS-CoV-2 Variants KP.1.1, LB.1, and KP.3.3 From Approved Monoclonal Antibodies

Planas,

Staropoli,

Planchais

et al. 2024

PAI

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Background: First-generation anti-SARS-CoV-2 monoclonal antibodies (mAbs) used for prophylaxis or therapeutic purposes in immunocompromised patients have been withdrawn because of the emergence of resistant Omicron variants. In 2024, 2 novel mAbs, VYD222/Pemivibart and AZD3152/Sipavibart, were approved by health authorities, but their activity against contemporary JN.1 sublineages is poorly characterized. Methods: We isolated authentic JN.1.1, KP.1.1, LB.1, and KP.3.3 viruses and evaluated their sensitivity to neutralization by these mAbs in 2 target cell lines. Results: Compared to ancestral strains, VYD222/Pemivibart remained moderately active against JN.1 subvariants, with a strong increase of 50% Inhibitory Concentration (IC50), reaching up to 3 to 15 µg/mL for KP.3.3. AZD3152/Sipavibart neutralized JN.1.1 but lost antiviral efficacy against KP.1.1, LB.1, and KP.3.3. Conclusions: Our results highlight the need for a close clinical monitoring of VYD222/Pemivibart and raise concerns about the clinical efficacy of AZD3152/Sipavibart.

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A potent, broadly neutralizing human monoclonal antibody that efficiently protects hACE2-transgenic mice from infection with the Wuhan, BA.5, and XBB.1.5 SARS-CoV-2 variants

Guselnikov,

Baranov,

Kulemzin

et al. 2024

Front. Immunol.

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The COVID-19 pandemic has uncovered the high genetic variability of the SARS-CoV-2 virus and its ability to evade the immune responses that were induced by earlier viral variants. Only a few monoclonal antibodies that have been reported to date are capable of neutralizing a broad spectrum of SARS-CoV-2 variants. Here, we report the isolation of a new broadly neutralizing human monoclonal antibody, iC1. The antibody was identified through sorting the SARS-CoV-1 RBD-stained individual B cells that were isolated from the blood of a vaccinated donor following a breakthrough infection. In vitro, iC1 potently neutralizes pseudoviruses expressing a wide range of SARS-CoV-2 Spike variants, including those of the XBB sublineage. In an hACE2-transgenic mouse model, iC1 provided effective protection against the Wuhan strain of the virus as well as the BA.5 and XBB.1.5 variants. Therefore, iC1 can be considered as a potential component of the broadly neutralizing antibody cocktails resisting the SARS-CoV-2 mutation escape.

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An update on the anti-spike monoclonal antibody pipeline for SARS-CoV-2

Cited by 3 publications

References 83 publications

Considerations for the development of monoclonal antibodies to address new viral variants in COVID-19

Considerations for the development of monoclonal antibodies to address new viral variants in COVID-19

Escape of SARS-CoV-2 Variants KP.1.1, LB.1, and KP.3.3 From Approved Monoclonal Antibodies

A potent, broadly neutralizing human monoclonal antibody that efficiently protects hACE2-transgenic mice from infection with the Wuhan, BA.5, and XBB.1.5 SARS-CoV-2 variants

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