Immune evasion of Omicron variants JN.1, KP.2, and KP.3 to the polyclonal and monoclonal antibodies from COVID-19 convalescents and vaccine recipients

Qian Wu; Hairuo Wu; Yabin Hu; Xingyu Zheng; Fangfang Chang; Yongchen Liu; Zhendong Pan; Qijie Wang; Fei Tang; Jun Qian; Yuezhou Li; Bin Huang; Keqiu Chen; Juan Xu; You Wang; Xiangping Xie; Ping Zhao; Xu Wu; Xiaowang Qu; Yi-Ping Li

doi:10.1016/j.antiviral.2025.106092

Immune evasion of Omicron variants JN.1, KP.2, and KP.3 to the polyclonal and monoclonal antibodies from COVID-19 convalescents and vaccine recipients

Antiviral Res. 2025 Jan 24:106092. doi: 10.1016/j.antiviral.2025.106092. Online ahead of print.

Authors

Qian Wu¹, Hairuo Wu¹, Yabin Hu², Xingyu Zheng³, Fangfang Chang¹, Yongchen Liu¹, Zhendong Pan⁴, Qijie Wang⁵, Fei Tang¹, Jun Qian¹, Yuezhou Li¹, Bin Huang¹, Keqiu Chen¹, Juan Xu¹, You Wang³, Xiangping Xie⁶, Ping Zhao⁴, Xu Wu⁷, Xiaowang Qu⁸, Yi-Ping Li⁹

Affiliations

¹ Institute of Human Virology, Zhongshan School of Medicine, and Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China.
² College of Basic Medical Sciences, Hengyang Medical School, University of South China & MOE Key Lab of Rare Pediatric Diseases, Hengyang 421001, China; Translational Medicine Institute, The First People's Hospital of Chenzhou, Hengyang Medical School, University of South China, Chenzhou 423000, China.
³ College of Basic Medical Sciences, Hengyang Medical School, University of South China & MOE Key Lab of Rare Pediatric Diseases, Hengyang 421001, China.
⁴ Department of Microbiology, Faculty of Naval Medicine, Naval Medical University, Shanghai, 200433, China.
⁵ The Central Hospital of Shaoyang, Shaoyang, 422099, China; Xinning Country People's Hospital, Shaoyang, 422099, China.
⁶ The Central Hospital of Shaoyang, Shaoyang, 422099, China.
⁷ Pulmonary and Critical Care Medicine, Hengyang Medical School, University of South China, No. 30, Jiefang Road, Shigu District, Hengyang, 421000, China. Electronic address: wx1048946906@126.com.
⁸ College of Basic Medical Sciences, Hengyang Medical School, University of South China & MOE Key Lab of Rare Pediatric Diseases, Hengyang 421001, China. Electronic address: quxiaowang@163.com.
⁹ Institute of Human Virology, Zhongshan School of Medicine, and Key Laboratory of Tropical Disease Control of Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China. Electronic address: lyiping@mail.sysu.edu.cn.

PMID: 39864525
DOI: 10.1016/j.antiviral.2025.106092

Abstract

The Omicron BA.2.86 subvariants, JN.1, KP.2, and KP.3, have become predominant globally, raising concerns about their immune evasion from vaccines and monoclonal antibody (mAb) treatments. These variants harbor more receptor-binding domain (RBD) mutations than the XBB and EG.5 sub-lineages, which are already known to compromise vaccine and therapeutic efficacy. We evaluated sera from individuals vaccinated with inactivated vaccines, with or without breakthrough infections, as well as COVID-19 convalescents. Our results showed a substantial decrease in serum neutralizing activity against the JN.1, KP.2, XBB.1.5, and EG.5.1 variants compared to BA.2. Additionally, we developed 19 neutralizing antibodies from memory B cells, with some retaining efficacy against earlier Omicron variants. However, potency was notably diminished against newer subvariants like BF.7, BQ.1, XBB.1.5, and BA.2.86. Among these, mAbs isolated from COVID-19 convalescents, particularly SA-3, exhibited exceptional potency across ten variants from BA.2 to KP.2, with IC50 values ranging from 0.006 to 2.546 μg/mL. However, SA-3 had lost neutralizing activity against the KP.3 due to the Q493E mutation, but become susceptible to neutralization by SA-6. In contrast, SA-6 was unable to neutralize KP.2 because of the presence of R346T mutation. Our findings underscore the importance of continuous surveillance of viral evolution and the need for updated vaccines and therapeutics to combat the ongoing evolution of SARS-CoV-2, particularly in the context of emerging variants that escape both vaccine-induced immunity and monoclonal antibody treatments.

Keywords: Broad cross-neutralizing activity; Inactivated vaccine; Monoclonal antibodies; Omicron variants; SARS-CoV-2.