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Infection and Immunity, February 2005, p. 981-989, Vol. 73, No. 2
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.2.981-989.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

PppA, a Surface-Exposed Protein of Streptococcus pneumoniae, Elicits Cross-Reactive Antibodies That Reduce Colonization in a Murine Intranasal Immunization and Challenge Model

Bruce A. Green,1* Ying Zhang,1 Amy W. Masi,1 Vicki Barniak,1 Michael Wetherell,1,{dagger} Robert P. Smith,1 Molakala S. Reddy,2 and Duzhang Zhu1

Wyeth Vaccines Research, Pearl River,1 Department of Oral Biology, University of Buffalo School of Dental Medicine, Buffalo, New York2

Received 24 June 2004/ Returned for modification 9 September 2004/ Accepted 11 October 2004

The multivalent pneumococcal conjugate vaccine is effective against both systemic disease and otitis media caused by serotypes contained in the vaccine. However, serotypes not covered by the present conjugate vaccine may still cause pneumococcal disease. To address these serotypes, and the remaining otitis media due to Streptococcus pneumoniae, efforts have been devoted to identifying protective protein antigens. Immunity to conserved surface proteins important for adhesion, nutrient acquisition, or other functions could result in a reduction of colonization and a lower disease potential. We have been searching for conserved surface-exposed proteins from S. pneumoniae that may be involved in pathogenesis to test as vaccine candidates. Here, an ~20-kDa protein that has significant homology to a nonheme iron-containing ferritin protein from Listeria innocua and other bactoferritins was identified as pneumococcal protective protein A (PppA). We expressed and purified recombinant PppA (rPppA) and evaluated its potential as a vaccine candidate. The antibodies elicited by purified rPppA were cross-reactive with PppA from multiple strains of S. pneumoniae and were directed against surface-exposed epitopes. Intranasal immunization of BALB/c mice with PppA protein and either a synthetic monophosphoryl lipid A analog, RC529AF, or a cholera toxin mutant, CT-E29H, used as an adjuvant reduced nasopharyngeal colonization in mice following intranasal challenge with a heterologous pneumococcal strain. PppA-specific systemic and local immunoglobulin G (IgG) and IgA antibody responses were induced. The antisera reacted with whole cells of a heterologous S. pneumoniae type 3 strain. These observations indicate that PppA may be a promising candidate for inclusion in a vaccine against pneumococcal otitis media.

* Corresponding author. Mailing address: 401 N. Middletown Rd., Bldg. 205/3104, Pearl River, NY 10965. Phone: (845) 602-2754. Fax: (845) 602-5536. E-mail: greenba{at}wyeth.com.

Editor: J. N. Weiser

{dagger} Present address: Genencor, Inc., Rochester, N.Y.

Infection and Immunity, February 2005, p. 981-989, Vol. 73, No. 2
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.2.981-989.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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