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Intradermal influenza vaccination in complete remission cancer patients: molecular insights

  • Davide Bedognetti1,
  • Maria Libera Ascierto1,
  • Marimo Sato-Matsushita1,
  • Elena Gugiatti2,
  • Carlotta Massucco2,
  • Simonetta Zupo2,
  • Antonio Di Meglio2,
  • Chiara Dellepiane2,
  • Mario Roberto Sertoli2,
  • Omar Racchi2,
  • Enrico Balleari2,
  • Valeria De Giorgi1,
  • Michele Sommariva1,
  • Paolo Durando2,
  • Manlio Ferrarini2,
  • Roberto Cacciani2,
  • Nicoletta Provinciali2,
  • Rocco Iudici2,
  • Cristiano Alicino2,
  • Ena Wang1,
  • Filippo Ansaldi2,
  • Francesco M Marincola3, 1 and
  • Andrea De Maria2
Journal for ImmunoTherapy of Cancer20131(Suppl 1):P197

Published: 7 November 2013


InfluenzaInfluenza VaccinationInnate ResponseVaccine AdministrationIntradermal Administration

We previously showed that long-lasting complete remission (CR) non-Hodgkin lymphoma (NHL) patients treated with rituximab-containing chemotherapy have an attenuated antibody response to virosomal (Bedognetti et al, J. Immunology, 2011) or MF-59 adjuvanted (Bedognetti et al, Blood, 2012) seasonal (or pandemic) influenza vaccine (as compared with healthy controls), associated with persistent CD27+ Memory B cell depletion and hypogammaglobulinemia. Here, we evaluated humoral and innate response to trivalent intradermal vaccination in NHL in CR previously treated with rituximab-containing chemotherapy (at least one year before vaccine administration), RIT group, and in CR cancer patients treated with chemotherapy without rituximab (at least one year before vaccine administration), Non-RIT group. Intradermal administration was chosen considering its promising data, compared to conventional intramuscular route, in terms of immunogenicity and safety. Humoral response was assessed by hemagglutinin inhibition assay on sera collected at time 0 (just before vaccination) and at time 28 (four weeks after vaccination). Innate response was assessed by whole-genome gene expression analysis (Affymetrix Humane Gene ST 1.0) on PBMC collected at time 0 and at time 1 (24 hours after vaccine administration). Patients treated with rituximab-containing chemotherapy had, overall, a lower antibody response, compared to patients treated with chemotherapy alone. Overall, intradermal vaccination induced dramatic changes in gene-expression profile already one day after vaccination. These changes underline the activation of IFN stimulated genes (eg, STAT1, STAT2, CXCL10, IDO1, GBP1) and modulation of NK-associated transcripts. In addition, pathway and gene-enrichment analysis show that RIT and non-RIT groups have different quantitative and qualitative transcriptomic changes 24 hours after vaccination administration. Concordantly with antibody-titer, the innate response was more intense in Non-RIT group compared with RIT group.

Authors’ Affiliations

DTM, NIH, Bethesda, USA
IRCCS San Martino-Ist, Genova, Italy
Sidra Medical and Research Centre, Doha, Qatar


© Bedognetti et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.