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Th17 responses to pneumococcus in blood and adenoidal cells in children

Research output: Contribution to journalArticle

  • Elizabeth H Oliver
  • C Pope
  • E Clarke
  • C Langton Hewer
  • A D Ogunniyi
  • J C Paton
  • T Mitchell
  • R Malley
  • A Finn
Original languageEnglish
Pages (from-to)213-225
Number of pages13
JournalClinical and Experimental Immunology
Volume195
Issue number2
Early online date31 Oct 2018
DOIs
DateAccepted/In press - 3 Oct 2018
DateE-pub ahead of print - 31 Oct 2018
DatePublished (current) - Feb 2019

Abstract

Pneumococcal infections cause a large global health burden, and the search for serotype-independent vaccines continues. Existing conjugate vaccines reduce nasopharyngeal colonization by target serotypes. Such mucosal effects of novel antigens may similarly be important. CD4 + Th17 cell-dependent, antibody-independent reductions in colonization and enhanced clearance have been described in mice. Here we describe the evaluation of T helper type 17 (Th17) cytokine responses to candidate pneumococcal protein vaccine antigens in human cell culture, using adenoidal and peripheral blood mononuclear cells. Optimal detection of interleukin (IL)-17A was at day 7, and of IL-22 at day 11, in these primary cell cultures. Removal of CD45RO + memory T cells abolished these responses. Age-associated increases in magnitude of responses were evident for IL-17A, but not IL-22, in adenoidal cells. There was a strong correlation between individual IL-17A and IL-22 responses after pneumococcal antigen stimulation (P < 0·015). Intracellular cytokine staining following phorbol myristate acetate (PMA)/ionomycin stimulation demonstrated that > 30% CD4 + T cells positive for IL-22 express the innate markers γδT cell receptor and/or CD56, with much lower proportions for IL-17A + cells (P < 0·001). Responses to several vaccine candidate antigens were observed but were consistently absent, particularly in blood, to PhtD (P < 0·0001), an antigen recently shown not to impact colonization in a clinical trial of a PhtD-containing conjugate vaccine in infants. The data presented and approach discussed have the potential to assist in the identification of novel vaccine antigens aimed at reducing pneumococcal carriage and transmission, thus improving the design of empirical clinical trials.

    Research areas

  • cytokines, human, T cells, vaccination

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    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Wiley at https://onlinelibrary.wiley.com/doi/full/10.1111/cei.13225 . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 862 KB, PDF document

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