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Infection and Immunity, December 2005, p. 7878-7886, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.7878-7886.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Active and Passive Intranasal Immunizations with Streptococcal Surface Protein C5a Peptidase Prevent Infection of Murine Nasal Mucosa-Associated Lymphoid Tissue, a Functional Homologue of Human Tonsils

Hae-Sun Park* and P. Patrick Cleary

Department of Microbiology, University of Minnesota Medical School, Minneapolis, Minnesota 55455

Received 14 April 2005/ Returned for modification 18 July 2005/ Accepted 29 August 2005

C5a peptidase, also called SCPA (surface-bound C5a peptidase), is a surface-bound protein on group A streptococci (GAS), etiologic agents for a variety of human diseases including pharyngitis, impetigo, toxic shock, and necrotizing fasciitis, as well as the postinfection sequelae rheumatic fever and rheumatic heart disease. This protein is highly conserved among different serotypes and is also expressed in human isolates of group B, C, and G streptococci. Human tonsils are the primary reservoirs for GAS, maintaining endemic disease across the globe. We recently reported that GAS preferentially target nasal mucosa-associated lymphoid tissue (NALT) in mice, a tissue functionally analogous to human tonsils. Experiments using a C5a peptidase loss-of-function mutant and an intranasal infection model showed that this protease is required for efficient colonization of NALT. An effective vaccine should prevent infection of this secondary lymphoid tissue; therefore, the potential of anti-SCPA antibodies to protect against streptococcal infection of NALT was investigated. Experiments showed that GAS colonization of NALT was significantly reduced following intranasal immunization of mice with recombinant SCPA protein administered alone or with cholera toxin, whereas a high degree of GAS colonization of NALT was observed in control mice immunized with phosphate-buffered saline only. Moreover, administration of anti-SCPA serum by the intranasal route protected mice against streptococcal infection. These results suggest that intranasal immunization with SCPA would prevent colonization and infection of human tonsils, thereby eliminating potential reservoirs that maintain endemic disease.

* Corresponding author. Mailing address: Department of Microbiology, University of Minnesota Medical School, 1460 Mayo Bldg., MMC196, 420 Delaware Street SE, Minneapolis, MN 55455. Phone: (612) 624-0622. Fax: (612) 626-0623. E-mail: hspark{at}lenti.med.umn.edu.

Editor: V. J. DiRita

Infection and Immunity, December 2005, p. 7878-7886, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.7878-7886.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Gleich-Theurer, U., Aymanns, S., Haas, G., Mauerer, S., Vogt, J., Spellerberg, B. (2009). Human Serum Induces Streptococcal C5a Peptidase Expression. Infect. Immun. 77: 3817-3825 [Abstract] [Full Text]  


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