Robust neutralizing antibody response to the XBB.1.5 trivalent recombinant protein vaccine booster

Dear Editor,The global prevalence of XBB subvariants,known for their significant immune evasion,has driven the development and adaptation of XBB vaccines.Monovalent XBB.1.5 mRNA vaccines have been developed and shown to provoke robust immune responses against XBB.1.5,EG.5.1,and BA.2.86 following vaccination.1 In June 2023,the XBB.1.5-recombinant COVID-19 trivalent(XBB.1.5+BA.5+Delta)protein vaccine(trivalent XBB.1.5 vaccine)(WestVac Biopharma Co.,Ltd.,China)was approved for emergency use against XBB subvariants.Although preliminary data from the manufacturer suggest neutralization of several earlier Omicron subvariants and XBB.1.5,there is limited real-world evidence,and persisting immune imprinting may affect the induction of antibodies against new SARS-CoV-2 sublineages,2 such as JN.1,which has increased transmissibility and the ability to evade immunity.3 Additionally,subsequent XBB infection after BA.5/BF.7 breakthrough infection does not efficiently induce humoral immunity against JN.1,4 raising questions about the ability of the trivalent XBB.1.5 vaccine to provide adequate protection against this lineage.We measured the neutralizing antibody responses in 32 individuals who experienced a BA.5/BF.7 breakthrough infection and a subsequent XBB infection before and after receiving the trivalent XBB.1.5 vaccination.The detailed demographic information of the study participants and their vaccination and infection histories are described in the Supplementary Methods.