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Infection and Immunity, November 2002, p. 6409-6415, Vol. 70, No. 11
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.11.6409-6415.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Immunization with C5a Peptidase or Peptidase-Type III Polysaccharide Conjugate Vaccines Enhances Clearance of Group B Streptococci from Lungs of Infected Mice

Qi Cheng,1 Steven Debol,1 Hong Lam,1 Ron Eby,2 Lorri Edwards,2 Yury Matsuka,2 Stephen B. Olmsted,2 and P. Patrick Cleary1*

Department of Microbiology, University of Minnesota, Minneapolis, Minnesota 55455,1 Wyeth-Lederle Vaccines, Rochester, New York 145862

Received 10 May 2002/ Returned for modification 17 July 2002/ Accepted 15 August 2002

Group B streptococci (GBS) are among the most common causes of life-threatening neonatal infections. Vaccine development since the late 1970s has focused on the capsular polysaccharides, but a safe, effective product is still not available. Our quest for a vaccine turned to the streptococcal C5a peptidase (SCPB). This surface protein is antigenically conserved across most if not all serotypes. A murine model was used to assess the impact of SCPB on clearance of GBS from the lungs of intranasally infected animals. Mutational inactivation of SCPB resulted in more-rapid clearance of streptococci from the lung. Immunization with recombinant SCPB alone or SCPB conjugated to type III capsular polysaccharide produced serotype-independent protection, which was evidenced by more-rapid clearance of the serotype VI strain from the lungs. Immunization of mice with tetanus toxoid-type III polysaccharide conjugate did not produce protection, confirming that protection induced by SCPB conjugates was independent of type III polysaccharide antigen. Histological evaluation of lungs from infected mice revealed that pathology in animals immunized with SCPB or SCPB conjugates was significantly less than that in animals immunized with a tetanus toxoid-polysaccharide conjugate. These experiments suggest that inclusion of C5a peptidase in a vaccine will both add another level to and broaden the spectrum of the protection of a polysaccharide vaccine.

* Corresponding author. Mailing address: Department of Microbiology, University of Minnesota, MMC 196, 420 Delaware St. S.E., Minneapolis, MN 55455. Phone: (612) 624-3932. Fax: (612) 626-0623. E-mail: cleary{at}lenti.med.umn.edu.

Editor: J. D. Clements

Infection and Immunity, November 2002, p. 6409-6415, Vol. 70, No. 11
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.11.6409-6415.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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