Sixth monovalent XBB.1.5 vaccine elicits robust immune response against emerging SARS-CoV-2 variants in heart transplant recipients

Abstract

Continued circulation of SARS-CoV-2 has driven the selection of variants with improved ability to escape pre-existing vaccine-induced responses, posing a persistent threat to heart transplant recipients (HTRs). The immunogenicity and safety of the updated XBB.1.5-containing monovalent vaccines are unknown. We prospectively enrolled 52 HTRs who had previously received a 5-dose ancestral-derived monovalent and bivalent mRNA vaccination schedule to receive the monovalent XBB.1.5 vaccine. Immunogenicity was evaluated using live virus micro-neutralization assays. The XBB.1.5 monovalent vaccine elicited potent and diverse neutralizing responses and broadened the reactivity spectrum to encompass newer strains, with the highest increase in neutralization activity being more pronounced against XBB.1.5 (15.8-fold) and JN.1 (13.3-fold) than against BA.5 (6.7-fold) and WT (4-fold). Notably, XBB.1.5 and JN.1 were resistant to neutralization by pre-vaccination sera. There were no safety concerns. Our findings support updating of COVID-19 vaccines to match antigenically divergent variants and exclude ancestral spike-antigen to protect HTRs.