Science translational medicineSep 3, 2025

The XBB.1.5 COVID-19 vaccine produces lasting antibodies against original and XBB.1.5 coronavirus spike proteins

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 7, 2026

Abstract

The XBB.1.5 COVID-19 vaccine induced durable antibody responses with half-lives of 703 days for WA1 and 531 days for XBB.1.5 IgG spike protein binding antibodies.

A single dose of the XBB.1.5 mRNA vaccine increased the magnitude and breadth of neutralizing antibodies against ancestral and variant SARS-CoV-2 strains.
IgG1 and IgG4 binding antibodies against the XBB.1.5 spike protein were significantly higher than those against the WA1 spike protein after vaccination.
High cross-reactivity of antibodies against both WA1 and XBB.1.5 strains was observed and remained durable over time.
Six months post-vaccination, neutralizing antibodies showed reduced effectiveness against circulating Omicron variants KP.2 and KP.3 compared to XBB.1.5.
Findings suggest that while the XBB.1.5 vaccine promotes stronger and longer-lasting antibody responses, emerging variants may still evade these defenses.

Simplified

The rapid emergence of divergent SARS-CoV-2 variants led to a 2023-2024 update of the COVID-19 mRNA vaccine to a monovalent version containing the XBB.1.5 SARS-CoV-2 spike antigen. To determine the durability and breadth of the antibody responses after immunization, we analyzed antibodies and memory B cells from 24 individuals before and after a single XBB.1.5 mRNA vaccine dose for up to 6 months. Using a live virus neutralization assay, we found that the XBB.1.5 vaccine improved the magnitude and breadth of antibody neutralizing activity against the ancestral SARS-CoV-2 strain (WA1), BA.5 strain, and XBB.1.5 Omicron variants. Durable WA1 and XBB.1.5 IgG spike protein binding antibodies were induced with an estimated half-life of 703 and 531 days (at day 120), respectively. There was a greater increase of IgG1 and IgG4 binding antibodies against the XBB.1.5 spike protein compared with the WA1 spike protein postvaccination. A high proportion of antibodies were cross-reactive against both WA1 and XBB.1.5 strains, as determined by serum depletion and memory B cell analysis, and this cross-reactivity was durable. Last, we evaluated the neutralizing activity of these antibodies against more contemporary circulating Omicron strains and observed reduced cross-reactivity to KP.2 and KP.3 compared with XBB.1.5 6 months after vaccination. These data show that the XBB.1.5 COVID-19 vaccine promotes more durable binding and neutralizing antibodies than prior ancestral WA1 or bivalent vaccines. However, divergent Omicron variants with mutations in the spike protein were able to evade these neutralizing antibodies, emphasizing the need for periodic consideration of COVID-19 vaccine reformulation.

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The XBB.1.5 COVID-19 vaccine produces lasting antibodies against original and XBB.1.5 coronavirus spike proteins

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