Abstract

BackgroundThe analysis of pre- and post-vaccination B-cell-associated cytokines might be useful in predicting the immunogenicity of seasonal trivalent influenza vaccine (TIV) in solid organ transplant (SOT) recipients. MethodsWe performed a subanalysis of a clinical trial that compared the safety and efficacy of high-dose intradermal (ID) versus intramuscular (IM) TIV in SOT recipients. Serum levels of selected cytokines (interferon [IFN]-γ, interleukin [IL]-2, IL-4, IL-5, IL-6, IL-12 and IL-21, and tumor necrosis factor [TNF]-α) were measured pre- and one month post-vaccination in 155 patients (with 84 and 71 receiving the ID and IM vaccines, respectively). Cytokine profiles were compared according to vaccine response (seroconversion [≥4-fold increase in hemagglutination inhibition antibody titers] to ≥1 influenza vaccine antigen). ResultsMean baseline IL-6 levels were higher (1.20 versus 0.65pg/mL; P-value=0.021) and IL-2 levels were lower (0.01 versus 0.50pg/mL; P-value=0.051) in patients achieving vaccine response. After adjusting for clinical variables, baseline IL-6/IL-2 ratio remained predictive of vaccine response (odds ratio per 10-unit increment: 1.06; 95% confidence interval: 1.02–1.10; P-value=0.002). Vaccination induced an increase in TNF-α (P-value <0.0001) and a decrease in IL-5 levels (P-value=0.0007). There were no significant differences in cytokine kinetics between vaccine responders and non-responders. Mean baseline TNF-α levels were higher in patients experiencing moderate-to-severe adverse events after vaccination (1.93 versus 1.72pg/mL; P-value=0.009). ConclusionsBaseline serum IL-6 and IL-2 levels, two cytokines that modulate the role of CD4+ T follicular helper cells and the terminal differentiation of B-cells, predict vaccine response in SOT recipients.

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