Matrix M™ adjuvanted virosomal H5N1 vaccine induces balanced Th1/Th2 CD4 + T cell responses in man

Gabriel K. Pedersen, Haakon Sjursen, Jane K. Nøstbakken, Åsne Jul-Larsen, Katja Hoschler, Rebecca J. Cox*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

T cellular responses play a significant role in mediating protective immune responses against influenza in humans. In the current study, we evaluated the ability of a candidate virosomal H5N1 vaccine adjuvanted with Matrix M™ to induce CD4 + and CD8 + T cell responses in a phase 1 clinical trial. We vaccinated 60 healthy adult volunteers (at days 0 and 21) with 30 μg haemagglutinin (HA) alone or 1.5, 7.5, or 30 μg HA formulated with Matrix M™. To evaluate the T cellular responses, lymphocytes were stimulated in vitro with homologous (A/Vietnam/1194/2004 [H5N1]) and heterologous H5N1 (A/Anhui/1/05 or A/Bar-headed Goose/Qinghai/1A/05) antigens. The antigen-specific cytokine responses were measured by intracellular cytokine staining and by multiplex (Luminex) assays. An increase in CD4 + Th1 and Th2 cytokines was detected 21 days after the first vaccine dose. No increase in Th cytokine responses was observed after the second dose, although it is possible that the cytokine levels peaked earlier than sampling point at day 42. Formulation with the Matrix M™ adjuvant augmented both the homologous and cross-reactive cytokine response. Antigen-specific CD8 + T cell responses were detected only in a few vaccinated individuals. The concentrations of Th1 and to a lesser extent, Th2 cytokines at 21 days post-vaccination correlated moderately with subsequent days 35 and 180 serological responses as measured by the microneutralisation, haemagglutination inhibition, and single radial hemolysis assays. Results presented here show that the virosomal H5N1 vaccine induced balanced Th1/Th2 cytokine responses and that Matrix M™ is a promising adjuvant for future development of candidate pandemic influenza vaccines.

Original languageEnglish
Pages (from-to)2408-2416
Number of pages9
JournalHuman Vaccines and Immunotherapeutics
Volume10
Issue number8
DOIs
Publication statusPublished - 1 Aug 2014

Bibliographical note

Funding Information:
This study was supported by the EU FP7 Univax (601738), RCN Globvac project (220670), the K.G. Jebsen Centre for Influenza Vaccine Research, and intramurally by the Influenza Centre, University of Bergen. The work in the UK was funded by the Health Protection Agency. We thank the Ministry of Health and Care Services, Norway, Crucell, The Netherlands for providing the vaccine, ISCONOVA, Uppsala, Sweden for providing the Matrix MTM adjuvant, Dr Vidadi Yusibov (Fraunhofer USA) for the H5N1 plant antigens and the staff at the Influenza Centre, Bergen for help with performing experiments.

Publisher Copyright:
© 2014 Landes Bioscience.

Keywords

  • CD4
  • CD8
  • Cytokine
  • H5N1
  • Human
  • Influenza
  • Matrix M
  • Th1
  • Th2
  • Vaccine

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