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Infection and Immunity, May 2009, p. 2076-2083, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01554-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Protection against Pneumococcal Colonization and Fatal Pneumonia by a Trivalent Conjugate of a Fusion Protein with the Cell Wall Polysaccharide{triangledown}

Ying-Jie Lu,1 Sophie Forte,1 Claudette M. Thompson,2 Porter W. Anderson,1 and Richard Malley1*

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, Boston, Massachusetts2

Received 22 December 2008/ Returned for modification 23 January 2009/ Accepted 19 February 2009

Cell wall polysaccharide (CWPS), pneumolysin, and surface adhesin A (PsaA) are antigens common to virtually all serotypes of Streptococcus pneumoniae (pneumococcus), and all have been studied separately for use in protection. Previously we showed that protection against nasopharyngeal (NP) colonization by intranasal vaccination of mice with killed pneumococci is mediated by TH17 cells and correlates with interleukin-17A (IL-17A) expression by T cells in vitro; we have also shown that CWPS and other species-common antigens protect against colonization by a similar mechanism. Here we made a fusion protein of PsaA with the pneumolysin nontoxic derivative PdT and then coupled CWPS to the fusion protein, aiming to enhance immune responses to all three antigens. When given intranasally with cholera toxin adjuvant, the fusion conjugate induced higher serum antibody titers and greater priming for IL-17A responses than an equimolar mixture of the three antigens. The conjugate administered intranasally protected mice against experimental NP colonization by a strain of serotype 6B, while mice immunized with the mixture or with bivalent conjugates were not protected. Subcutaneous immunization with the conjugate and alum adjuvant likewise induced higher antibody titers than the mixture, primed for IL-17A responses, and reduced colonization. The conjugate, but not the antigen mixture, fully protected mice from fatal pneumonia caused by a highly virulent serotype 3 strain. Thus, a covalent construct of three antigens common to all serotypes exhibits protection with both mucosal and systemic administration.

* 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

{triangledown} Published ahead of print on 2 March 2009.

Editor: J. N. Weiser

Infection and Immunity, May 2009, p. 2076-2083, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01554-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Xin, W., Li, Y., Mo, H., Roland, K. L., Curtiss, R. III (2009). PspA Family Fusion Proteins Delivered by Attenuated Salmonella enterica Serovar Typhimurium Extend and Enhance Protection against Streptococcus pneumoniae. Infect. Immun. 77: 4518-4528 [Abstract] [Full Text]  


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