Antipneumococcal effects of C-reactive protein and monoclonal antibodies to pneumococcal cell wall and capsular antigens

Abstract

Antibodies to pneumococcal capsular polysaccharides are well known for their ability to protect against pneumococcal infection. Recent studies indicate that antibodies to cell wall antigens, including pneumococcal surface protein A and the phosphocholine (PC) determinant of teichoic acids as well as human C-reactive protein (which also binds to PC), can protect mice against pneumococcal infection. In the present study we compared the protective effects of these agents as measured by mouse protection, the blood bactericidal assay, and clearance of pneumococci from the blood and peritoneal cavity. Our findings extend previous results indicating that human C-reactive protein and antibodies to noncapsular antigens are generally less protective than anticapsular antibodies. The new results obtained indicate the following: (i) mouse protection studies with intraperitoneal and intravenous infections provide very similar results; (ii) monoclonal immunoglobulin G2a (IgG2a) antibodies to PC, like IgG1, IgG2b, and IgG3 antibodies to PC, are highly protective against pneumococcal infection in mice; (iii) human antibody to PC is able to protect against pneumococcal infection in mice; (iv) antibodies to PspA are effective at mediating blood and peritoneal clearance of pneumococci; (v) complement is required for the in vivo protective effects of both IgG and IgM antibodies to PC; (vi) IgG1, IgG2b, and IgG3 anti-PC antibodies all mediate complement-dependent lysis of PC-conjugated erythrocytes; and (vii) antibodies and human C-reactive proteins that are reactive with capsular antigens but not cell wall antigens are able to mediate significant antibacterial activity in the blood bactericidal assay.

Immunogenicity of Streptococcus pneumoniae type 14 capsular polysaccharide: influence of carriers and adjuvants on isotype distribution

“…However, a large increase in IgG3 antibody was not observed in previous studies. IgG3 is normally present only in very low concentrations and tends to be produced following immunization with polysaccharides, which are thymus-independent antigens (7)(8)(9).…”

“…Briles et al showed that IgG3 antibody is especially protective against pneumococcal infections in mice (7). In later studies, however, they showed that the other IgG isotypes can also be protective (8,9). Studies on the role of various isotypes of antibody in protection have been hampered by the paucity of experimental models.…”

“…This is potentially important because the isotypes of IgG antibody differ in protective efficacy for many infections (11,30,34). The IgG2a and IgG3 isotypes have been reported to be particularly effective in conferring protection against S. pneumoniae (7)(8)(9). We have demonstrated recently that the isotype of antibody produced by hapten or peptide conjugates is influenced by the carrier.…”

B and CD4+ T‐cell expression of TLR2 is critical for optimal induction of a T‐cell‐dependent humoral immune response to intact Streptococcus pneumoniae

“…Pn also elicits antibody specific for various structures on the bacterial surface, which includes the pneumococcal capsular polysaccharide (PPS) 7, the cell wall C‐polysaccharide (teichoic acid), including its phosphorylcholine (PC) moieties 8 and various pneumococcal proteins including pneumococcal surface protein (PspA) 9. Adaptive immunity to pneumococcus is largely conferred by these antibodies, which synergize with the innate immune system to confer markedly enhanced host protection 10.…”

Difference in Binding of Killed and Live Streptococcus pneumoniae Serotypes by C‐Reactive Protein

“…In the presence of CRP, complement-dependent opsonization of S. pneumoniae type 27 and pneumococcal polysaccharide-coated erythrocytes has been reported [8,9]. However, enhanced phagocytosis was only found for live S. pneumoniae type 27 with capsular bound CRP and C3 [10] and not for live S. pneumoniae type 4 which binds C3 in the cell wall in the presence of CRP [11].…”