Activity of Research-Grade Pemivibart against Recent SARS-CoV-2 JN.1 Sublineages

Qian Wang; Yicheng Guo; Jerren Ho; David D. Ho

Qian Wang, Yicheng Guo, Jerren Ho, David D Ho

New England Journal of Medicine, doi:10.1056/nejmc2410203

To the Editor: In March 2024, pemivibart (Invivyd) was authorized for emergency use as preexposure prophylaxis against coronavirus disease 2019 (Covid-19) for immunocompromised patients who might not have a robust response to vaccines. 1 This human monoclonal antibody was derived from ADG-2, an antibody directed at the receptor-binding domain class 1/4 region in the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This antibody had previously shown protective efficacy against SARS-CoV-2 infection. 2 However, ADG-2 lost virus-neutralizing activity against the omicron variant and its subsequent subvariants. Nine mutations (five in the heavy chain and four in the light chain) were introduced to create pemivibart, which showed greater breadth in neutralizing recent SARS-CoV-2 strains. 3 The JN.1 subvariant of SARS-CoV-2 emerged in late 2023 and rapidly became dominant globally. In the past 6 months, JN.1 has continued to evolve, giving rise to multiple sublineages with unique spike mutations (Fig. S1A in the Supplementary Appendix, available with the full text of this letter at NEJM.org). KP.2 was a JN.1 progeny that appeared, but it was later outcompeted by KP.3, with both sublineages gradually displacing the original JN.1 (Fig. S1B ). More recently, KP.3.1.1, KP.2.3, and LB.1 have emerged, each with independent development of a deletion of S31 in the N-terminal domain of the spike protein; KP.3.1.1 is now a fast-growing sublineage worldwide. In this study, we assessed the effect of recent SARS-CoV-2 evolution on the neutralizing activity of a version of pemivibart that we synthesized in our laboratory. We constructed pseudoviruses for JN.1, KP.2, KP.3, KP.2.3, KP.3.1.1, and LB.1 and subjected them to neutralization assays, as described previously. 4 Our laboratory-synthesized pemivibart neutralized both JN.1 and KP.2 in vitro with similar activity, whereas its potency was decreased modestly against LB.1, KP.2.3, and KP.3 and substantially against KP.3.1.1 (Fig. 1A ). The 50% inhibitory concentration (IC 50 ) of our laboratory-synthesized pemivibart against KP.3.1.1 was approximately 4.0 μg per milliliter or approximately 25 times as high as that against JN.1 (Fig. 1B ), an increase that could reduce the protec-

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