Mario Fernández-Ruiz1, Atul Humar1, Aliyah Baluch2, Shanil Keshwani1, Shahid Husain1, Deepali Kumar3. 1. Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada. 2. Division of Infectious Diseases, Moffitt Cancer Center, Tampa, FL, United States. 3. Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada. Electronic address: Deepali.Kumar@uhn.ca.
Abstract
BACKGROUND: The 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. METHODS: We 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). RESULTS:Mean 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). CONCLUSIONS:Baseline 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.
RCT Entities:
BACKGROUND: The 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. METHODS: We 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). RESULTS: Mean 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). CONCLUSIONS: Baseline 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.
Authors: Andrew H Karaba; Xianming Zhu; Sarah E Benner; Olivia Akinde; Yolanda Eby; Kristy H Wang; Sharada Saraf; Jacqueline M Garonzik-Wang; Sabra L Klein; Justin R Bailey; Andrea L Cox; Joel N Blankson; Christine M Durand; Dorry L Segev; William A Werbel; Aaron A R Tobian Journal: Transplantation Date: 2022-04-01 Impact factor: 4.939