Effect of Immunosuppression on Th2 and B-cell Responses to Influenza Vaccination

BACKGROUND: Influenza vaccine immunogenicity is suboptimal in immunocompromised patients. However, there are limited data on the interplay of Tand Bcell responses to vaccination with simultaneous immunosuppression. METHODS: We collected peripheral blood mononuclear cells from transplant recipients before and 1 month after seasonal influenza vaccination. Before and after vaccination, H1N1-specific Tand B-cell activation were quantified with flow cytometry. We also developed a mathematical model using Tand B-cell markers and mycophenolate mofetil (MMF) dosage. RESULTS: In the 47 patients analyzed, seroconversion to H1N1 antigen was demonstrated in 34%. H1N1-specific interleukin 4 (IL-4)-producing CD4(+) T-cell frequencies increased significantly after vaccination in 53% of patients. Prevaccine expression of H1N1-induced HLA-DR and CD86 on B cells was high in patients who seroconverted. Seroconversion against H1N1 was strongly associated with HLA-DR expression on B cells, which was dependent on the increase between prevaccine and postvaccine H1N1-specific IL-4(+)CD4(+) T cells (R(2) = 0.35). High doses of MMF (� 2 g/d) led to lower seroconversion rates, smaller increase in H1N1-specific IL-4(+)CD4(+) T cells, and reduced HLA-DR expression on B cells. The mathematical model incorporating a MMF-inhibited positive feedback loop between H1N1-specific IL-4(+)CD4(+) T cells and HLA-DR expression on B cells captured seroconversion with high specificity. CONCLUSIONS: Seroconversion is associated with influenza-specific T-helper 2 and B-cell activation and seems to be modulated by MMF. DOI: https://doi.org/10.1093/infdis/jiv015 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-122339 Accepted Version Originally published at: Egli, Adrian; Humar, Atul; Widmer, Lukas A; Lisboa, Luiz F; Santer, Deanna M; Mueller, Thomas; Stelling, Joerg; Baluch, Aliyah; O’Shea, Daire; Houghton, Michael; Kumar, Deepali (2015). Effect of immunosuppression on T-helper 2 and B-cell responses to influenza vaccination. Journal of Infectious Diseases, 212(1):137-146. DOI: https://doi.org/10.1093/infdis/jiv015 Ac ce pte d M an us cri pt 1 © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e‐mail: [email protected]. Effect of Immunosuppression on Th2 and B-cell Responses to Influenza Vaccination Adrian Egli, Atul Humar, Lukas A. Widmer, Luiz F. Lisboa, Deanna M. Santer, Thomas Mueller, Joerg Stelling, Aliyah Baluch, Daire O’Shea, Michael Houghton, Deepali Kumar Infection Biology, Department Biomedicine, University of Basel, Switzerland Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Canada Transplant Infectious Diseases and Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada Department of Biosystems Science and Engineering (D-BSSE), ETH Zurich, and Swiss Institute of Bioinformatics, Basel, Switzerland Division of Nephrology, University Hospital Zurich, Switzerland Division of Infectious Diseases, Moffitt Cancer Center, Tampa, Florida Correspondence: Adrian Egli, MD PhD, Infection Biology Lab, Department Biomedicine, University Basel, Petersgraben 4, 4031 Basel, Switzerland, Tel: +41 61 556 57 49, Email: [email protected] Co-Corresponding Author: Deepali Kumar MD, University Health Network, PMB 11174, 585 University Avenue, Toronto, Ontario, Canada, M5G 2N2, Tel: 416-340-4241, Fax: 416-340-4043 Journal of Infectious Diseases Advance Access published January 14, 2015 at Z entraibliothek on Feruary 5, 2016 http://jidrdjournals.org/ D ow nladed from