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T cell memory response to pneumococcal protein antigens in an area of high pneumococcal carriage and disease

Mureithi, Marianne W.; Ota, Martin O.; Mitchell, Timothy J.; Williams, Neil A.; Adegbola, Richard A.; Heyderman, Robert S.; Finn, Adam; Zhang, Qibo; Davenport, Victoria

Authors

Marianne W. Mureithi

Martin O. Ota

Timothy J. Mitchell

Neil A. Williams

Richard A. Adegbola

Robert S. Heyderman

Adam Finn

Qibo Zhang

Victoria Davenport Victoria.Davenport@uwe.ac.uk
Associate Director (Biological & Biomedical Science)



Abstract

Background. Streptococcus pneumoniae is a leading cause of vaccine-preventable disease worldwide. Pneumococcal protein antigens are currently under study as components of potential vaccines that offer protection against multiple serotypes. We have therefore characterized T cell pneumococcal immunity acquired through asymptomatic carriage. Methods. Peripheral blood mononuclear cells from 40 healthy Gambian adults were stimulated with supernatants derived from S. pneumoniae strain (D39), 2 isogenic mutant strains lacking either pneumolysin or choline binding protein A, and recombinant pneumolysin. Immune responses were measured by cellular proliferation and by interleukin-10 (IL-10) and interferon-γ (IFN-γ) enzyme-linked immunosorbent spot and bioplex cytokine assays. Nasopharyngeal swabs were cultured to determine carriage rates. Results. S. pneumoniae nasopharyngeal carriage was detected in 60% of individuals. Both effector and resting (or central) CD4 - T cell memory were frequently present to a range of pneumococcal antigens. However, the level of the effector memory response did not relate to current nasopharyngeal carriage. Pneumolysin was not immunodominant in these T cell responses but induced a distinct proinflammatory profile (high IFN-7, IL-12[p40], and L-17 levels and low IL-10 and IL-13 levels). Conclusions. In this population, T cell-mediated immunological memory potentially capable of pathogen clearance and immune surveillance is common but is not associated with the absolute interruption of pneumococcal carriage. How this naturally acquired immune memory influences pneumococcal vaccine efficacy remains to be determined. © 2009 by the Infectious Diseases Society of America. All rights reserved.

Citation

Heyderman, R. S., Adegbola, R. A., Williams, N. A., Mitchell, T. J., Ota, M. O., Mureithi, M. W., …Davenport, V. (2009). T cell memory response to pneumococcal protein antigens in an area of high pneumococcal carriage and disease. Journal of Infectious Diseases, 200(5), 783-793. https://doi.org/10.1086/605023

Journal Article Type Article
Publication Date Sep 1, 2009
Journal Journal of Infectious Diseases
Print ISSN 0022-1899
Publisher Oxford University Press (OUP)
Peer Reviewed Peer Reviewed
Volume 200
Issue 5
Pages 783-793
DOI https://doi.org/10.1086/605023
Keywords T cell memory
Public URL https://uwe-repository.worktribe.com/output/1004651
Publisher URL http://dx.doi.org/10.1086/605023