Neutralizing antibody evasion of SARS-CoV-2 JN.1 derivatives KP.3, KP.3.1.1, LB.1, and XEC

Kaori Sano; Kei Miyakawa; Hideaki Kato; Yayoi Kimura; Atsushi Goto; Akihide Ryo; Shinji Watanabe; Hideki Hasegawa

doi:10.1016/j.vaccine.2025.127472

Neutralizing antibody evasion of SARS-CoV-2 JN.1 derivatives KP.3, KP.3.1.1, LB.1, and XEC

Vaccine. 2025 Aug 30:62:127472. doi: 10.1016/j.vaccine.2025.127472. Epub 2025 Jul 9.

Authors

Kaori Sano¹, Kei Miyakawa², Hideaki Kato³, Yayoi Kimura⁴, Atsushi Goto⁵, Akihide Ryo⁶, Shinji Watanabe⁷, Hideki Hasegawa⁸

Affiliations

¹ Influenza Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan.
² Influenza Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan; AIDS Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan; Department of Microbiology, Yokohama City University School of Medicine, Yokohama, Japan. Electronic address: keim@niid.go.jp.
³ Infection Prevention and Control Department, Yokohama City University Hospital, Yokohama, Japan; Emerging Infectious Diseases Research Center, Advanced Medical Research Center, Yokohama City University, Yokohama, Japan.
⁴ Advanced Medical Research Center, Yokohama City University, Yokohama, Japan; Emerging Infectious Diseases Research Center, Advanced Medical Research Center, Yokohama City University, Yokohama, Japan.
⁵ Department of Public Health, Yokohama City University School of Medicine, Yokohama, Japan; Emerging Infectious Diseases Research Center, Advanced Medical Research Center, Yokohama City University, Yokohama, Japan.
⁶ Department of Microbiology, Yokohama City University School of Medicine, Yokohama, Japan; Department of Bioinformatics and Integrative Omics, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan.
⁷ Influenza Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan. Electronic address: sw@niid.go.jp.
⁸ Influenza Research Center, National Institute of Infectious Diseases, Japan Institute for Health Security, Tokyo, Japan; Institute for Vaccine Research and Development, Hokkaido University, Sapporo, Japan. Electronic address: hasegawa@niid.go.jp.

PMID: 40639176
DOI: 10.1016/j.vaccine.2025.127472

Abstract

The emergence of SARS-CoV-2 variants poses ongoing challenges to vaccine efficacy. We evaluated neutralizing antibody responses against JN.1 and its derivatives (KP.3, KP.3.1.1, LB.1, and XEC) in healthcare workers who received seven doses of BNT162b2, including the XBB.1.5 monovalent vaccine. In COVID-19-naïve individuals, KP.3.1.1 and LB.1 showed substantial immune escape, whereas previously infected individuals maintained neutralization activity against all variants. We also demonstrated that JN.1-based immunization induces robust cross-neutralizing activity against emerging variants. A single amino acid deletion at position 31 in the spike protein may be associated with enhanced immune evasion. These findings support the potential effectiveness of JN.1-based vaccines while highlighting the need for continued surveillance and vaccine optimization.

Keywords: COVID-19; Immune escape; JN.1; KP.3.1.1; Omicron; XEC.

MeSH terms

Adult
Antibodies, Neutralizing* / blood
Antibodies, Neutralizing* / immunology
Antibodies, Viral* / blood
Antibodies, Viral* / immunology
BNT162 Vaccine / immunology
COVID-19 Vaccines* / administration & dosage
COVID-19 Vaccines* / immunology
COVID-19* / immunology
COVID-19* / prevention & control
COVID-19* / virology
Female
Health Personnel
Humans
Immune Evasion*
Male
Middle Aged
Neutralization Tests
SARS-CoV-2* / genetics
SARS-CoV-2* / immunology
Spike Glycoprotein, Coronavirus / genetics
Spike Glycoprotein, Coronavirus / immunology

Substances

Antibodies, Neutralizing
Antibodies, Viral
Spike Glycoprotein, Coronavirus
COVID-19 Vaccines
BNT162 Vaccine
spike protein, SARS-CoV-2

Supplementary concepts

SARS-CoV-2 variants