1159. IL-17A and IL-22 Production by In Vitro Paediatric Adenoidal and Blood Lymphocyte Cultures in Response to Pneumococcal Vaccine Candidates  – a Potential Tool for Measuring Mucosal Immunity
Session: Poster Abstract Session: Innate and Adaptive Immunity to Infections
Saturday, October 22, 2011
Room: Poster Hall B1
Handouts
  • IDSA 2011 A.Finn poster.pdf (415.9 kB)
  • Background: 

    IL-17A generation by CD4+ T cells can mediate antibody-independent mucosal immune nasopharyngeal clearance of pneumococci in mice. This mechanism may also affect other bacterial species & human immune cells produce IL-17A in response to pneumococcal antigens. Candidate protein vaccines against nasal bacteria, by inducing mucosal immune responses might exert indirect effects &/or herd protection. A tool for assessing such responses may assist evaluation of such vaccines if such responses are quantitatively predictive of vaccine effects on colonisation at the individual or population level.

    Methods: 

    We evaluated IL-17A and IL-22 induction by pneumococcal whole cell antigen (WCA) & individual recombinant pneumococcal protein antigens in adenoidal mononuclear cell (AMNC), peripheral blood mononuclear cell (PBMC) & whole blood cultures from 28 children aged 1-14.

    Results: 

    Important differences in the cytokine responses between these distinct cell preparations, & between antigens, have been observed. IL-17A generation by PBMC in response to stimulation with the single antigens CbpA, PsaA and PspA, & to our WCA were significantly greater than the response detected to media alone (P<0.0001), whereas another protein antigen we tested, PhtD, did not generate an IL-17A response above background.   However, when we tested these antigens in AMNC cultures, only WCA elicited an IL-17A response significantly greater than our background response (p=0.03).  Furthermore, similar results were observed when we examined IL-22 generation.   Additionally, we were able to detect IL-17A in response to WCA in whole blood (n=11), although responses were greatly reduced in comparison with those detected in isolated PBMC or AMNC (whole blood 0-43pg/ml (median 4pg/ml), PBMC 15–707pg/ml (median 202pg/ml), AMNC 79–1040pg/ml (median 148pg/ml).

    Conclusion: 

    The relationship between intercurrent nasal carriage & cytokine generation & the requirement for antigen presentation (rather than solely innate mechanisms of cellular activation) are also under investigation.  These studies are providing new insights into specific cell-mediated immunity to pneumococcal antigens in children & may contribute towards methodology for vaccine evaluation in the future.


    Subject Category: E. Innate and adaptive immunity to infections, including vaccine immunology

    Caroline Pope, PhD1, Elizabeth Oliver, BSc1, Christopher Wright, PhD1, Ed Clarke, MD PhD1, Richard Malley, MD2 and Adam Finn, MD, PhD3, (1)Cellular & Molecular Medicine, University of Bristol, Bristol, United Kingdom, (2)Division of Infectious Diseases, Department of Medicine, Children’s Hospital Boston and Harvard Medical School, Boston, MA, (3)School of Clinical Sciences, University of Bristol, Bristol, United Kingdom

    Disclosures:

    C. Pope, None

    E. Oliver, None

    C. Wright, None

    E. Clarke, None

    R. Malley, None

    A. Finn, None

    Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.