title: T(H)17-based vaccine design for prevention of Streptococcus pneumoniae colonization.
abstract: Streptococcus pneumoniae is a leading cause of mortality in young children. While successful conjugate polysaccharide vaccines exist, a less expensive serotype-independent protein-based pneumococcal vaccine offers a major advancement for preventing life-threatening pneumococcal infections, particularly in developing nations. IL-17A-secreting CD4+ T cells (T(H)17) mediate resistance to mucosal colonization by multiple pathogens including S. pneumoniae. Screening an expression library containing >96% of predicted pneumococcal proteins, we identified antigens recognized by T(H)17 cells from mice immune to pneumococcal colonization. The identified antigens also elicited IL-17A secretion from colonized mouse splenocytes and human PBMCs suggesting that similar responses are primed during natural exposure. Immunization of two mouse strains with identified antigens provided protection from pneumococcal colonization that was significantly diminished in animals treated with blocking CD4 or IL-17A antibodies. This work demonstrates the potential of proteomic screening approaches to identify specific antigens for the design of subunit vaccines against mucosal pathogens via harnessing T(H)17-mediated immunity.
authors.affiliation: Division of Infectious Diseases, Children's Hospital Boston, Harvard Medical School, MA 02115, USA.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Moffitt
authors.forename: Todd M
authors.initials: TM
authors.lastname: Gierahn
authors.forename: Ying-jie
authors.initials: YJ
authors.lastname: Lu
authors.forename: Paulo
authors.initials: P
authors.lastname: Gouveia
authors.forename: Mark
authors.initials: M
authors.lastname: Alderson
authors.forename: Jessica Baker
authors.initials: JB
authors.lastname: Flechtner
authors.forename: Darren E
authors.initials: DE
authors.lastname: Higgins
authors.forename: Richard
authors.initials: R
authors.lastname: Malley
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D006801:Humans; D007114:Immunization; D020381:Interleukin-17 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011008:Pneumococcal Infections / Q000276:immunology / Q000382:microbiology* / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology* / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D020381:Interleukin-17; D022242:Pneumococcal Vaccines