mBioNov 25, 2025

Antibody responses to SARS-CoV-2 variants after KP.2 single-strain mRNA vaccination

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jan 7, 2026

Abstract

Neutralizing antibody responses in 56 adults showed substantial reductions against emerging Omicron variants following KP.2 vaccination.

KP.2 vaccination enhanced neutralization against homologous variants but provided limited protection against emerging Omicron variants.
All exposure groups exhibited reduced neutralizing activity against variants such as LP.8.1, LF.7.1, NB.1.8.1, XFG, and BA.3.2.
Exposure history influenced neutralization breadth, with those vaccinated only showing better cross-neutralization than individuals with hybrid immunity.
Antigenic cartography revealed significant antigenic distances between KP.2 and emerging variants, indicating potential immune escape.
These findings underscore ongoing challenges in maintaining vaccine effectiveness against evolving SARS-CoV-2 variants.

Simplified

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in antigenically distinct variants that challenge vaccine-induced immunity. The KP.2 monovalent mRNA vaccine was deployed in 2024 to address immune escape by emerging SARS-CoV-2 subvariants. We assessed neutralizing antibody responses in 56 adults with varied exposure histories following KP.2 vaccination against emerging variants including LP.8.1, LF.7.1, NB.1.8.1, XFG, and BA.3.2. While KP.2 vaccination enhanced neutralization against homologous variants, substantial reductions in neutralizing activity were observed against emerging Omicron variants across all exposure groups. Exposure history showed some influence on neutralization breadth, with self-reported vaccination-only participants exhibiting better cross-neutralization compared to individuals with hybrid immunity. Antigenic cartography revealed substantial antigenic distances between KP.2 and emerging variants, highlighting significant immune escape potential that threatens vaccine protection.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, producing variants that escape vaccine-induced immunity. The current work shows that KP.2 monovalent vaccination provides limited protection against antigenically distant Omicron variants (LP.8.1, LF.7.1, NB.1.8.1, XFG and BA.3.2). These findings highlight the ongoing challenge of maintaining vaccine effectiveness against evolving SARS-CoV-2 variants and argue for continuous updating of vaccines.

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Competing interests

The Icahn School of Medicine at Mount Sinai has filed patent applications regarding influenza virus vaccines on which F.K. is listed as inventor. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays, NDV-based SARS-CoV-2 vaccines, influenza virus vaccines, and influenza virus therapeutics which list F.K. as co-inventor. V.S. is also listed on the SARS-CoV-2 serological assays patent. F.K. has received royalty payments from some of these patents. Mount Sinai has spun out a company, Castlevax, to develop SARS-CoV-2 vaccines. F.K. is a co-founder and scientific advisory board member of Castlevax. F.K. has consulted for Merck, GSK, Sanofi, Curevac, Gritstone, Seqirus, and Pfizer and is currently consulting for 3rd Rock Ventures and Avimex. The Krammer laboratory is also collaborating with Dynavax on influenza vaccine development. The Simon and van Bakel labs collaborate with Sanofi Pasteur on pathogen surveillance.

PubMed

Antibody responses to SARS-CoV-2 variants after KP.2 single-strain mRNA vaccination

Abstract

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Competing interests

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