J Korean Med Sci.  2023 Jul;38(27):e205. 10.3346/jkms.2023.38.e205.

Loss of Neutralizing Activity of Tixagevimab/Cilgavimab (Evusheld™) Against Omicron BN.1, a Dominant Circulating Strain Following BA.5 During the Seventh Domestic Outbreak in Korea in Early 2023

• Yang J
• Hyeon S
• Baek JY
• Kang MS
• Lee KY
• Lee YH
• Huh K
• Cho SY
• Kang CI
• Chung DR
• Peck KR
• Won G
• Lee HW
• Kim K
• Hwang I
• Lee SY
• Kim BC
• Lee Yk
• Ko JH

• KMID: 2544411
• DOI: http://doi.org/10.3346/jkms.2023.38.e205

Abstract

Tixagevimab/cilgavimab is a monoclonal antibody used to prevent coronavirus disease 2019 among immunocompromised hosts and maintained neutralizing activity against early omicron variants. Omicron BN.1 became a dominant circulating strain in Korea early 2023, but its susceptibility to tixagevimab/cilgavimab is unclear. We conducted plaque reduction neutralization test (PRNT) against BN.1 in a prospective cohort (14 patients and 30 specimens). BN.1 PRNT was conducted for one- and three-months after tixagevimab/ cilgavimab administration and the average PRNT ND ₅₀ of each point was lower than the positive cut-off value of 20 (12.9 ± 4.5 and 13.2 ± 4.2, respectively, P = 0.825). In the paired analyses, tixagevimab/cilgavimab-administered sera could not actively neutralize BN.1 (PRNT ND ₅₀ 11.5 ± 2.9, P = 0.001), compared with the reserved activity against BA.5 (ND ₅₀ 310.5 ± 180.4). Unlike virus-like particle assay, tixagevimab/cilgavimab was not active against BN.1 in neutralizing assay, and would not be effective in the present predominance of BA.2.75 sublineages.

Keyword

COVID-19; SARS-CoV-2; Evusheld; Neutralizing Antibody; BN.1 Variant

Figure

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  Fig. 1 Schematic view of the study and antibody kinetics after administration of tixagevimab/cilgavimab 600 mg. (A) Schematic view of the study, presented along with SARS-CoV-2 variant distribution in Korea from January 2022 to March 2023. We revised and extended the period of the Fig. 1 in the previously published article.1 After administration of tixagevimab/cilgavimab 600 mg, log10 Sab BAU/mL values exhibited a linearly waning kinetics (B). Compared to the peak point measured one month after admininistartion, a significant reduction of Sab titers was noticed after three months (C). PRNT ND50 titers against BN.1 were low at both points without significant difference, most of which were under the positive cut-off value of 20 (D). When the values of the peak point were compared, PRNT ND50 against BN.1 were significantly lower than that against BA.5 (E) unlike previously reported pseudotyped VLPs assay.6IC = immunocompromised, Sab = anti-spike protein antibody, BAU = binding antibody unit, PRNT = plaque reduction neutralization test, ND50 = 50% neutralizing dose, VLP = virus-like particles, ns = not significant.aExcept for BN.1, the proportion of which is presented separately.***P < 0.001.

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