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Infection and Immunity, April 2006, p. 2187-2195, Vol. 74, No. 4
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.4.2187-2195.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Antibody-Independent, Interleukin-17A-Mediated, Cross-Serotype Immunity to Pneumococci in Mice Immunized Intranasally with the Cell Wall Polysaccharide

Richard Malley,1* Amit Srivastava,1 Marc Lipsitch,2 Claudette M. Thompson,2 Claire Watkins,1 Arthur Tzianabos,3 and Porter W. Anderson4

Division of Infectious Diseases, Department of Medicine, Children's Hospital and Harvard Medical School,1 Departments of Epidemiology and Immunology and Infectious Diseases, Harvard School of Public Health,2 Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts,3 Department of Pediatrics, University of Rochester, Rochester, New York4

Received 30 November 2005/ Returned for modification 10 January 2006/ Accepted 30 January 2006

Serotype-specific immunity to Streptococcus pneumoniae is conferred by antibodies to the capsular polysaccharides, which define the 90 known serotypes. 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 S. pneumoniae of serotype 6B. This immunity could be induced in mice congenitally lacking immunoglobulin but was dependent upon CD4+ 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 S. pneumoniae.

* Corresponding author. Mailing address: Division of Infectious Diseases, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115. Phone: (617) 919-2902. Fax: (617) 730-0255. E-mail: Richard.Malley{at}childrens.harvard.edu.

Editor: J. N. Weiser

Infection and Immunity, April 2006, p. 2187-2195, Vol. 74, No. 4
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.4.2187-2195.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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