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Whether antibody to the species-common cell wall polysaccharide (C-Ps) is protective has been a matter of controversy. Here we show that C-Ps given intranasally with mucosal adjuvant increased the resistance of mice to experimental nasopharyngeal colonization by capsulated<jats:italic>S. pneumoniae<\/jats:italic>of serotype 6B. This immunity could be induced in mice congenitally lacking immunoglobulin but was dependent upon CD4<jats:sup>+<\/jats:sup>T cells. Elimination of the charged amino group on the polymer backbone by N acetylation of C-Ps reduced the immunity, as did treatment of the mice with antibody to the cytokine interleukin-17A at the time of challenge, both consistent with the hypothesis of T-cell activation due to the zwitterionic motif of the polymer. C-Ps also protected in a model of fatal aspiration pneumonia by heavily capsulated serotype 3. These findings suggest a novel immunization strategy against<jats:italic>S. pneumoniae<\/jats:italic>.<\/jats:p>","DOI":"10.1128\/iai.74.4.2187-2195.2006","type":"journal-article","created":{"date-parts":[[2006,3,21]],"date-time":"2006-03-21T23:12:50Z","timestamp":1142982770000},"page":"2187-2195","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":147,"title":["Antibody-Independent, Interleukin-17A-Mediated, Cross-Serotype Immunity to Pneumococci in Mice Immunized Intranasally with the Cell Wall Polysaccharide"],"prefix":"10.1128","volume":"74","author":[{"given":"Richard","family":"Malley","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Children's Hospital and Harvard Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Children's Hospital and Harvard Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Lipsitch","sequence":"additional","affiliation":[{"name":"Departments of Epidemiology and Immunology and Infectious Diseases, Harvard School of Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudette M.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Departments of Epidemiology and Immunology and Infectious Diseases, Harvard School of Public Health"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Watkins","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Children's Hospital and Harvard Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Tzianabos","sequence":"additional","affiliation":[{"name":"Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Porter W.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Rochester, Rochester, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.31.1.160-168.1981"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.5.2526-2534.2002"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.12.5255-5262.1996"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00006454-200003000-00003"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.128.6.1385"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(99)00511-3"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1086\/376571"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.153.3.694"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj1100573"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.4.1958"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.05.001"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/174.6.1271"},{"key":"e_1_3_2_14_2","unstructured":"Streptococcus pneumoniae: molecular biology & mechanisms of disease 2000"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1086\/424517"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1086\/341658"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.9.3913"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.10.5541-5548.2003"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.1.2.227"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1254"},{"key":"e_1_3_2_21_2","unstructured":"Janeway C. 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