LP.8.1-directed recombinant protein COVID-19 vaccine S-268025, formulated with squalene-based adjuvant A-910823, elicits robust immunogenicity and neutralizing breadth in mice.

SARS-CoV-2 continues to evolve by repeatedly undergoing antigenic mutations and evolving into different lineages, evading host immunity. Currently, viruses derived from the JN.1 lineages such as XFG and NB.1.8.1 strains have continued to spread globally, and the BA.3.2.2 strain has also been detected as a new lineage that may have acquired immune evasion capabilities. Here, we demonstrated that a recombinant protein vaccine S-268025, formulated with the LP.8.1 strain antigen and squalene adjuvant A-910823, induced potent serum neutralizing antibody titers against LP.8.1, XFG, NB.1.8.1, and PQ.2.8.1 variants in mice. This neutralizing breadth was comparable to that of a recombinant protein vaccine formulated with the XFG antigen. Intriguingly, the serum neutralizing antibody titers, elicited by the recombinant protein vaccine formulated with the BA.3.2.2 antigen, were shown to differ from those induced by the LP.8.1 and XFG vaccines. Furthermore, the priming series of vaccination with the LP.8.1 vaccine had an impact on the booster immunization with the BA.3.2.2 vaccine, and limited levels of NAbs induction against the BA.3.2.2 pseudovirus were detected. A line of evidence from nonclinical findings supports the efficacy of the LP.8.1 vaccine in COVID-19 vaccine regimens for the 2026-27 seasons.