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Infection and Immunity, April 2001, p. 2302-2308, Vol. 69, No. 4
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.4.2302-2308.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Antibody against Surface-Bound C5a Peptidase Is Opsonic and Initiates Macrophage Killing of Group B Streptococci

Qi Cheng,1 Brian Carlson,1 Sub Pillai,2 Ron Eby,2 Lorri Edwards,2 Stephen B. Olmsted,2 and Patrick Cleary1,*

Department of Microbiology, University of Minnesota, Minneapolis, Minnesota 55455,1 and Wyeth-Lederle Vaccine, Rochester, New York2

Received 5 October 2000/Returned for modification 29 November 2000/Accepted 8 January 2001

The capsular polysaccharides of group B streptococci (GBS) are a primary focus of vaccine development. Immunogenicity and long-lasting protection are best achieved by conjugating polysaccharides to a T-cell-dependent protein antigen. Streptococcal C5a peptidase (SCPB) is a conserved surface protein that is expressed by all streptococcal serotypes tested to date, and it is a possible carrier protein that could itself induce a protective immune response. Clearance of GBS from lungs, mucosal surfaces, or blood probably depends on the opsonophagocytic response of tissue-specific macrophages and polymorphonuclear leukocytes (PMNs). In this study, we examined the potential of antibody directed against SCPB from a serotype II strain to enhance the capacity of mouse bone marrow macrophages (from primary cultures) and human PMNs in whole blood to kill GBS in vitro. Our experiments demonstrated that Streptococcus serotypes Ia, Ib, II, III, and V, preopsonized with anti-SCPB antibody, were killed more rapidly by cultured macrophages and PMNs in whole blood than were nonopsonized GBS. The increased rate of killing was accompanied by an increased macrophage oxidative burst. Furthermore, opsonization was serotype transparent. Immunization with SCPB conjugated to capsular polysaccharide type III produced polysaccharide-specific antibodies. It is interesting that this antiserum promoted serotype-independent killing of streptococci. These data support the use of SCPB in a GBS polysaccharide conjugate vaccine. SCPB not only enhanced the immunogenicity of polysaccharide components of the vaccine, but it might also induce additional serotype-independent protective antibodies.

* Corresponding author. Mailing address: Box 196 UMHC, Dept. of Microbiology, University of Minnesota, Minneapolis, MN 55455. Phone: (612) 624-6190. Fax: (612) 626-0623. E-mail: cleary{at}lenti.med.umn.edu.

Infection and Immunity, April 2001, p. 2302-2308, Vol. 69, No. 4
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.4.2302-2308.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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