SARS-CoV-2 mRNA XBB1.5 vaccine immunogenicity in kidney transplant recipients.

BACKGROUND

Despite the reduced clinical severity of Omicron SARS-CoV-2 variants compared to earlier lineages, kidney transplant recipients (KTR) continue to experience higher SARS-CoV-2 mortality rates than the general population. Seroconversion rates following SARS-CoV-2 mRNA vaccination remain lower in KTR after three vaccine injections.

METHODS

We evaluated anti-SARS-CoV-2 neutralizing antibody activity and cellular responses, as well as whole blood gene expression profiles after XBB.1.5 mRNA vaccination boost in a cohort of KTR.

RESULTS

We demonstrated that XBB.1.5 mRNA boosting increased both the magnitude and frequency of neutralizing antibody responses against different SARS-CoV-2 variants and found that the neutralizing activity against Wuhan strain or XBB.1.5 subvariant was driven by different anti-Spike binding IgG subclasses. We also demonstrated that Spike-specific CD4⁺ T-cell responses were significantly boosted against Wuhan strain and XBB.1.5 subvariant one month following XBB.1.5 mRNA vaccination. Lastly, we showed that XBB.1.5 boost induced overexpression of genes associated with type I IFN and innate immune responses at day 1, but also activated T and NK-cells at day 3 that persist at day 7 post-vaccination.

CONCLUSIONS

Globally, increasing the number of vaccine injections using updated XBB.1.5 mRNA vaccine enhance anti-SARS-CoV-2 immune responses in KTR. However, the monovalent XBB.1.5 mRNA vaccine boost elicited recall of cross-reacting immune responses against the original Wuhan Spike without a clear advantage against Omicron subvariants, consistent with a predominant immunological imprinting.