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

Abstract

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-celldependent 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.

The Group B Streptococcal C5a Peptidase Is Both a Specific Protease and an Invasin

“…Moreover, the O90R(del) strain is cleared from lungs of infected mice much faster than the SCPB ϩ parent culture (unpublished data). SCPB is highly immunogenic, and antibodies against the protein facilitate killing of GBS by primary cultures of bone marrow-derived macrophages and by neutrophils (5). The experiments described here demonstrate that SCPB is also an invasin, suggesting yet another mechanism by which the SCP can contribute to the virulence of GBS.…”

“…Our laboratory showed that anti-SCPB opsonized GBS in phagocytosis assays (5). For this reason rabbit anti-SCPB was tested for its capacity to inhibit adherence and invasion of epithelial cells by GBS.…”

“…Immunization of mice with SCPA enhanced elimination of GAS following intranasal infection. The role of SCPB in virulence of GBS has not been extensively investigated; however, antibody directed against recombinant SCPB was found to be opsonic and to induce macrophage killing of GBS (5). Although vaccine development has focused primarily on the capsular polysaccharide (10), these studies suggested that SCPB protein could possibly induce serotype-independent immunity to infection (5).…”

“…The role of SCPB in virulence of GBS has not been extensively investigated; however, antibody directed against recombinant SCPB was found to be opsonic and to induce macrophage killing of GBS (5). Although vaccine development has focused primarily on the capsular polysaccharide (10), these studies suggested that SCPB protein could possibly induce serotype-independent immunity to infection (5). Bohnsack et al showed that SCPBdeficient GBS were cleared more rapidly from mice that were supplemented with human C5a following lung infection (2).…”

Current Understanding of Streptococcal Urinary Tract Infection

“…-hemolysin has a role in early but not late PCD and its expression is abolished by glucose (Fettucciari et al, 2000, Ulett et al, 2003. Several virulence factors of GBS including LTA, -hemolysin, C5a peptidase and the R protein/antigen are involved in recognition by host cells and inducing or evading immune www.intechopen.com responses (Cheng et al, 2001, Fasola et al, 1996, Henneke et al, 2005. The proficiency of GBS recognition by macrophages is considered a crucial component of early immune responses against the bacteria (Chattopadhyay et al, 2011, Franke-Ullmann et al, 1996, Jonsson et al, 1985, Sherman et al, 1992, Sibille&Reynolds, 1990).…”