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Published on: September 7, 2022
Th17 responses to pneumococcus in blood and adenoidal cells in children
1School of Cellular and Molecular Medicine, Biomedical Sciences Building, University of Bristol, Bristol, UK.
Insights
Researchers evaluated T helper type 17 (Th17) cell cytokine responses to pneumococcal vaccine antigens in human cells. This study helps identify new vaccine targets to reduce pneumococcal infections and transmission.
Area of Science:
- Immunology
- Vaccinology
Background:
- Pneumococcal infections present a significant global health challenge, driving the need for serotype-independent vaccines.
- Current conjugate vaccines reduce colonization by specific serotypes, but mucosal effects of new antigens are crucial.
- T helper type 17 (Th17) cell responses, independent of antibodies, have shown promise in reducing pneumococcal colonization in mouse models.
Purpose of the Study:
- To evaluate T helper type 17 (Th17) cytokine responses to candidate pneumococcal protein vaccine antigens in human cell cultures.
- To investigate the kinetics and characteristics of interleukin (IL)-17A and IL-22 responses in adenoidal and peripheral blood mononuclear cells.
- To assess the potential of these responses in identifying novel vaccine antigens for reducing pneumococcal carriage.
Main Methods:
- Human adenoidal and peripheral blood mononuclear cells were cultured and stimulated with pneumococcal antigens.
- Interleukin (IL)-17A and IL-22 production was measured over time (days 7 and 11).
- T cell populations (CD45RO+, CD4+, γδTCR+, CD56+) and cytokine expression were analyzed using intracellular cytokine staining and flow cytometry.
Main Results:
- Optimal detection of IL-17A at day 7 and IL-22 at day 11 in primary cell cultures.
- Removal of CD45RO+ memory T cells abolished Th17 cytokine responses.
- Age-associated increases in IL-17A responses were observed in adenoidal cells, with a strong correlation between IL-17A and IL-22 responses.
- A significant proportion of IL-22+ CD4+ T cells expressed innate markers (γδTCR and/or CD56), unlike IL-17A+ cells.
- Responses to most candidate antigens were detected, but notably absent for PhtD, particularly in blood.
Conclusions:
- The study provides a framework for evaluating Th17 cytokine responses to novel pneumococcal vaccine antigens in human cells.
- The findings suggest that PhtD may not be an effective antigen for inducing protective Th17 responses relevant to colonization.
- This approach can aid in the selection of vaccine antigens that induce mucosal immunity, potentially reducing pneumococcal carriage and transmission.
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.
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