Bivalent mRNA vaccine booster enhances immunity against XBB.1.5 more effectively than breakthrough infection in K18-hACE2 mice.

ABSTRACT: The rapid emergence of SARS-CoV-2 Omicron subvariants, including the highly immune-evasive XBB.1.5 lineage, continues to challenge vaccine effectiveness. We evaluated immune responses and protection against XBB.1.5 challenge in K18-hACE2 mice receiving two or three doses of a bivalent mRNA vaccine (encoding Wuhan-1 and Omicron BA.4/5 spike) or two doses followed by intranasal XBB.1.5 exposure. Homologous boosting with bivalent vaccine induced stronger neutralizing antibody and cellular immune responses than breakthrough infection against the antigenically distant XBB.1.5 variant. A two-dose series alone protected mice from severe disease, but boosting further enhanced protection, reducing lung viral RNA and inflammation. Although productive infection following intranasal exposure was not c

SUBMITTER: Linger ME 

PROVIDER: S-EPMC12481084 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature