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[Preprint]. 2025 Sep 19:2025.08.24.25333689.
doi: 10.1101/2025.08.24.25333689.

Antibody responses to SARS-CoV-2 variants LP.8.1, LF.7.1, NB.1.8.1, XFG and BA.3.2 following KP.2 monovalent mRNA vaccination

Anass Abbad  1   2 , Brian Lerman  1   2 , Jordan Ehrenhaus  1   2 , Brian Monahan  1   2 , Gagandeep Singh  1   2 , Adria Wilson  1   2 , Stefan Slamanig  1 , Ashley Aracena  1   2 , Neko Lyttle  1   2 , Jessica Nardulli  1   2 , Keith Farrugia  3 , Zain Khalil  3 , Ana Silvia Gonzalez-Reiche  3 , Emilia Mia Sordillo  4 , Weina Sun  1 , Harm M van Bakel  3 , Viviana Simon  1   2   3   4   5 , Florian Krammer  1   2   4   6   7
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Free PMC article

Antibody responses to SARS-CoV-2 variants LP.8.1, LF.7.1, NB.1.8.1, XFG and BA.3.2 following KP.2 monovalent mRNA vaccination

Anass Abbad et al. medRxiv. .
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Abstract

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, dramatic 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. Overall, our data suggest that KP.2 boosting predominantly enhances cross-reactive responses imprinted by previously encountered spike antigens, with limited adaptation to antigenically drifted variants.

Keywords: Antigenic cartography; COVID-19; Omicron; SARS-CoV-2; mRNA vaccine.

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Conflict of interest statement

Declaration of interests FK declares the following conflicts of interest. The Icahn School of Medicine at Mount Sinai has filed patent applications regarding influenza virus vaccines on which FK 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 FK as co-inventor. Dr. Simon is also listed on the SARS-CoV-2 serological assays patent. FK has received royalty payments from some of these patents. Mount Sinai has spun out a company, Castlevax, to develop SARS-CoV-2 vaccines. FK is co-founder and scientific advisory board member of Castlevax. FK 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.

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