Monoclonal antibodies against protease-sensitive pneumococcal antigens can protect mice from fatal infection with Streptococcus pneumoniae.

Abstract

Monoclonal antibodies were raised against surface determinants of Streptococcus pneumoniae by hyperimmunizing X-linked immunodeficient (xid) CBA/N mice with the heat-killed rough strain R36A. 17 hybridomas produced antibody that bound intact R36A and did not cross-react with phosphocholine, an antigen common in the cell wall of all S. pneumoniae. The antibody produced by at least two of these hybridomas, Xi64 (IgM) and Xi126 (IgG2b), could protect mice from a lethal intravenous challenge of type 3 S. pneumoniae strains WU2 and A66 and of the type 2 strain D39. The minimum amount of antibody required to protect xid mice from 100 WU2 was 4.5 micrograms/mouse for Xi64 and 2.6 micrograms/mouse for Xi126,. Free phosphocholine, C-polysaccharide, and type 3 capsular polysaccharide all failed to inhibit the binding of Xi64 or Xi126 to R36A. These antibodies appeared to bind surface polypeptides, since treatment of R36A with either pepsin or trypsin, or of R36A lysate with trypsin, effectively eliminated the ability of Xi64 and Xi126 to bind antigens in these preparations. Binding studies indicated that these two antibodies recognized different epitopes that were expressed on several but not all serotypes of pneumococci.

Differences of Pathophysiology in Experimental Meningitis Caused by Three Strains of Streptococcus Pneumoniae

“…Obviously, many bacterial components (e.g., enzymes [48], surface proteins [49]) could be important in modulating the disease caused by a specific strain. In light of the likely complexity of the interaction between microorganisms and host, the role of any putative virulence factor should ideally be defined by studying isogenic strains differing only in this variable.…”

Neural Signaling in the Spleen Controls B-Cell Responses to Blood-Borne Antigen

“…Streptococcus pneumonia strains R363 or ATCC 6303 were grown and inactivated as described previously (27). Briefly, R363 bacteria were grown to log phase in Todd Hewitt media containing 0.5% yeast extract and blood agar for 24 h at 3°C.…”

Genetic Alteration of Capsule Type but Not PspA Type Affects Accessibility of Surface-Bound Complement and Surface Antigens ofStreptococcus pneumoniae

“…However, PspA-elicited protection against the capsule type 2 strain D39 is poor, even when immunization is with PspA obtained from D39 derivatives (4,30,32,34). These same PspAs elicit protection against a wide variety of strains, including the capsule type 3 strain WU2 (4,32,34). The poor protection against D39 is consistent with the observation that PspA Ϫ mutants of D39 remain virulent, whereas the absence of PspA in WU2 results in avirulence (5,36,47; Abeyta and Yother, unpublished data).…”

“…Subsequent analyses of the sequences encoding the N-terminal halves of the proteins resulted in assignment of PspAs to three families and further subdivision into six clades (21). In general, PspAs from one serotype can elicit protection against strains representing different capsule and PspA types, although the levels of protection may differ between strains (4,30,32,34). However, PspA-elicited protection against the capsule type 2 strain D39 is poor, even when immunization is with PspA obtained from D39 derivatives (4,30,32,34).…”

“…In general, PspAs from one serotype can elicit protection against strains representing different capsule and PspA types, although the levels of protection may differ between strains (4,30,32,34). However, PspA-elicited protection against the capsule type 2 strain D39 is poor, even when immunization is with PspA obtained from D39 derivatives (4,30,32,34). These same PspAs elicit protection against a wide variety of strains, including the capsule type 3 strain WU2 (4,32,34).…”