T cell memory response to pneumococcal protein antigens in an area of high pneumococcal carriage and disease.
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-gamma (IFN-gamma) 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-gamma, 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.
Mureithi
Marianne W
MW
Bacterial Diseases Programme, Medical Research Council Laboratories, Banjul, Gambia. mmureithi@partners.org
Finn
Adam
A
Ota
Martin O
MO
Zhang
Qibo
Q
Davenport
Victoria
V
Mitchell
Timothy J
TJ
Williams
Neil A
NA
Adegbola
Richard A
RA
Heyderman
Robert S
RS
D000293:Adolescent; D000328:Adult; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D001769:Blood / Q000276:immunology; D002353:Carrier State / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D005714:Gambia; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009305:Nasopharynx / Q000382:microbiology; D011008:Pneumococcal Infections / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016753:Interleukin-10; D007371:Interferon-gamma