Antiviral humoral immunity against SARS-CoV-2 omicron subvariants induced by XBB.1.5 monovalent vaccine in infection-naive and XBB-infected individuals

To control infection with SARS-CoV-2 omicron XBB subvariants, the XBB.1.5 monovalent mRNA vaccine has been available since September, 2023. However, we have found that natural infection with XBB subvariants, including XBB.1.5, does not efficiently induce humoral immunity against the infecting XBB subvariants.1,  2,  3 These observations raise the possibility that the XBB.1.5 monovalent vaccine might not be able to efficiently induce humoral immunity against emerging SARS-CoV-2 variants, including a variety of XBB subvariants (XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1, and HK.3) as well as BA.2.86. To address this possibility, we collected two types of sera from individuals vaccinated with the XBB.1.5 vaccine: those who had not been previously infected with SARS-CoV-2 (n=9; figure A) and those who had been infected with XBB subvariants prior to XBB.1.5 vaccination (n=10; figure B). We collected sera before and 3–4 weeks after vaccination, and then performed a neutralisation assay using these sera and pseudoviruses. As expected, XBB.1.5 vaccine sera with previous XBB infection efficiently (1·8-fold to 3·6-fold) boosted antiviral humoral immunity against all variants tested with statistical significance (figure B). Importantly, in the case of the XBB.1.5 vaccine sera without previous infection, XBB.1.5 vaccine also efficiently induced antiviral activity (2·1-fold to 3·9-fold) against all variants tested with statistical significance (figure A). These observations suggest that a single dose of XBB.1.5 monovalent vaccine potentially induces antiviral humoral immunity against XBB subvariants as well as BA.2.86 without previous infection.