Cell reportsOct 15, 2025

How SARS-CoV-2 LP.8.1.1, NB.1.8.1, XFG, and similar subvariants avoid antibodies and bind to human receptors

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 7, 2026

Abstract

Serum neutralizing antibody titers against several SARS-CoV-2 subvariants were similar to those against XEC in 40 adults.

SARS-CoV-2 Omicron subvariants LP.8.1 and LP.8.1.1 outcompeted JN.1 subvariants KP.3.1.1 and XEC.
NB.1.8.1 and XFG have become dominant variants.
Neutralization studies indicated that NB.1.8.1 and XFG are more evasive to serum neutralization than LP.8.1.1.
Different monoclonal antibody classes were evaded by LP.8.1, XFG, MC.10.1, and LF.7.2.1.
LP.8.1 exhibited the highest receptor-binding affinity among the tested variants, which may explain its rise.
The expansion of NB.1.8.1 and XFG is associated with enhanced antibody evasion.

Simplified

SARS-CoV-2 continues to evolve, causing waves of infections. It is critical to understand the features of the virus that explain its growth advantages. Recently, SARS-CoV-2 Omicron JN.1 subvariants KP.3.1.1 and XEC were outcompeted by LP.8.1 and LP.8.1.1. Other subvariants, including LF.7.2.1 and MC.10.1, were also under monitoring. Subsequently, NB.1.8.1 and XFG became dominant. We found that serum neutralizing antibody titers against LP.8.1, LP.8.1.1, LF.7, LF.7.2.1, and MC.10.1 were similar to XEC in 40 adults, including KP.2 monovalent mRNA vaccine recipients. NB.1.8.1 and XFG were more evasive of serum neutralization than LP.8.1.1. Neutralization by 12 monoclonal antibodies (mAbs) revealed that LP.8.1 and XFG, MC.10.1 and NB.1.8.1, and LF.7.2.1 evade different mAb classes. Lastly, the receptor-binding affinity of LP.8.1 was the highest among the tested viruses. Unlike most prior SARS-CoV-2 sublineage evolutionary trajectories, receptor-binding affinity better explained the rise of LP.8.1, while expansion of NB.1.8.1 and XFG appears correlated with enhanced antibody evasion.

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Competing interests

Declaration of interests D.D.H. co-founded TaiMed Biologics and RenBio, and he serves as a consultant for WuXi Biologics and Brii Biosciences and is a board director at Vicarious Surgical. A.G. served as a member of the scientific advisory board for Janssen Pharmaceuticals and has consulted and serves on a scientific advisory board for Sanofi Pasteur.

PubMed

How SARS-CoV-2 LP.8.1.1, NB.1.8.1, XFG, and similar subvariants avoid antibodies and bind to human receptors

Abstract

Full Text

Funding

Competing interests

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