Do Existing COVID-19 Vaccines Need to Be Updated in 2025?

Abstract COVID-19 vaccines have been updated each year since 2022 to improve protection against evolving SARS-CoV-2 variants. However, it is unclear whether a reformulation will be necessary for 2025. KP.2-based monovalent COVID-19 mRNA vaccines (KP.2 MV) were authorized for use in 2024, and they conferred substantial protection against hospitalizations caused by viral variants that emerged and dominated later, such as KP.3.1.1 and XEC. Today, LP.8.1 and its subvariant LP.8.1.1 have become dominant worldwide, particularly so in North America. Other variants, such as the LF.7 subvariant LF.7.2.1, have emerged with a growth advantage in Asia. To characterize the antigenicity of LP.8.1, LP.8.1.1, LF.7, LF.7.2.1, and another variant under monitoring, MC.10.1, we tested serum samples from 20 individuals who recently received KP.2 MV in neutralization assays against JN.1, KP.2, KP.3, KP.3.1.1, XEC, LP.8.1, LP.8.1.1, LF.7, LF.7.2.1, or MC.10.1 pseudoviruses. Serum neutralizing antibody titers against LP.8.1, LP.8.1.1, LF.7, LF.7.2.1, and MC.10.1 were comparable to those against KP.3.1.1 and XEC, indicating that LP.8.1.1 and other recently dominant subvariants are antigenically similar to their predecessors. Therefore, the currently authorized KP.2 MV may not need to be updated for 2025, if the vaccine manufacturers could demonstrate comparable immunogenicity for KP.2 MV and LP.8.1-based mRNA vaccines and, of course, in the absence of an antigenically divergent SARS-CoV-2 variant emerging. Competing Interest Statement D.D.H. co-founded TaiMed Biologics and RenBio, and he serves as a consultant for WuXi Biologics and Brii Biosciences and is a board director at Vicarious Surgical. A.G. served as a member of the scientific advisory board for Janssen Pharmaceuticals and has consulted and serves on a scientific advisory board for Sanofi Pasteur. The remaining authors declare no conflicts of interest. Footnotes Additional pseudovirus neutralization assays against a broader set of currently dominant or concerning SARS-CoV-2 viral variants, using samples from an enlarged cohort. Prevalence and structural diagram panels also updated accordingly. The overall conclusion remains concordant with the first version of the preprint: circulating variants are antigenically similar in the serum of KP.2-directed vaccine recipients, and therefore it may be acceptable to use KP.2-directed vaccine boosters in 2025, as well.