Amato, N. J. | bioRxiv Science

bioRxiv2025

mRNA-1273.251 and mRNA-1283.251 vaccines expressing SARS-CoV-2 variant LP.8.1 antigens broadly neutralize contemporary JN.1-lineage viruses

The continued evolution of the SARS-CoV-2 Omicron JN.1 lineage has led to the emergence of antigenically distinct subvariants including KP.2, KP.3, XEC, and LP.8.1, which became the dominant strains in the Americas and Europe by mid-2025. LP.8.1 was designated a Variant Under Monitoring by the WHO in January 2025 due to its potential to displace prior circulating variants. Informed by early growth modeling and antigenic analysis, we selected LP.8.1 as a candidate strain for the 2025-2026 vaccine season. Here, we describe the development of updated LP.8.1-matched mRNA vaccine compositions encoding either the full-length spike protein for mRNA-1273 (monovalent) or the membrane-anchored receptor-binding and N-terminal domains for the mRNA-1283 vaccine. Initial in vitro characterization, including structural analysis, demonstrated robust antigen expression and intact antigenic features. Immunogenicity of both vaccines were evaluated in murine models following immunization as either a primary series in naive animals or as a booster dose. LP.8.1-matched vaccines elicited strong neutralizing antibody responses against the homologous LP.8.1 strain and more recently emerging JN.1-lineage subvariants, including XFG and NB.1.8.1. Notably, the mRNA-1283 vaccine expressing LP.8.1 induced higher mean neutralization titers than the mRNA-1273 version across multiple variants. These data demonstrate the immunogenicity and breadth of both LP.8.1-based mRNA-1273 and mRNA-1283 vaccines in the context of ongoing JN.1 lineage evolution and support the selection of LP.8.1 as the updated vaccine antigen for the 2025-2026 season.

immunology↗

bioRxiv2022

Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA.5 Omicron variant

The emergence of SARS-CoV-2 variants in the Omicron lineage with large numbers of substitutions in the spike protein that can evade antibody neutralization has resulted in diminished vaccine efficacy and persistent transmission. One strategy to broaden vaccine-induced immunity is to administer bivalent vaccines that encode for spike proteins from both historical and newly-emerged variant strains. Here, we evaluated the immunogenicity and protective efficacy of two bivalent vaccines that recently were authorized for use in Europe and the United States and contain two mRNAs encoding Wuhan-1 and either BA.1 (mRNA-1273.214) or BA.4/5 (mRNA-1273.222) spike proteins. As a primary immunization series in BALB/c mice, both bivalent vaccines induced broader neutralizing antibody responses than the constituent monovalent vaccines (mRNA-1273 [Wuhan-1], mRNA-1273.529 [BA.1], and mRNA-1273-045 [BA.4/5]). When administered to K18-hACE2 transgenic mice as a booster at 7 months after the primary vaccination series with mRNA-1273, the bivalent vaccines induced greater breadth and magnitude of neutralizing antibodies compared to an mRNA-1273 booster. Moreover, the response in bivalent vaccine-boosted mice was associated with increased protection against BA.5 infection and inflammation in the lung. Thus, boosting with bivalent Omicron-based mRNA-1273.214 or mRNA-1273.222 vaccines enhances immunogenicity and protection against currently circulating SARS-CoV-2 strains.

microbiology↗