Protective Effects of Polyclonal Sera and of Monoclonal Antibodies Active to Salmonella minnesota Re595 Lipopolysaccharide during Experimental Endotoxemia

Abstract

Mice were passively immunized with sera from blood donors active for rough lipopolysaccharides (LPS), the J5 (Rc chemotype) mutant of Escherichia coli O111:B4, and the Re595 (Re chemotype) mutant of Salmonella minnesota. All protected the mice against lethal challenge with smooth E. coli WF96 LPS, E. coli and Salmonella rough mutant LPS, or free lipid A. Epitopes recognized by monoclonal antibodies (MAbs) reacting with the LPS of S. minnesota Re595 or lipid A were localized in the 2-keto-3-deoxy-D-manno-octulosonic acid (KDO) region and on lipid A. Core-reactive MAbs reacted with their homologous Re LPS and with free lipid A. One, GL11, cross-reacted with the KDO alone. MAbs GL6, GL11, L.4, L.6, and L.8 protected the actinomycin D-sensitized mice against the lethal effects of LPS from E. coli WF96, Salmonella enteritidis, E. coli J5, S. minnesota Re595, and free lipid A. The GL11 antibody was also protective when injected after LPS challenge. These results indicate that antibodies directed against the core glycolipid of S. minnesota Re595 LPS may be useful as an additive form of therapy that may enable decreased mortality during gram-negative bacterial sepsis.

Review: Evidence against the hypothesis that antibodies to the inner core of lipopolysaccharides in antisera raised by immunization with enterobacterial deep-rough mutants confer broad-spectrum protection during Gram-negative bacterial sepsis

“…153 The protective serum fractions, however, failed to provide significant protection against the S-form LPS of S. enteriditis. In an earlier section, we have discussed the evidence that E. coli 07:K1 possesses rough or semirough LPS, rather than the S-form type.…”

“…48 Nys et al reported that J5 and R595 rabbit antisera protected actinomycin D-sensitized mice against lethality from E. coli 07 LPS, but not from S. enteriditis LPS. 153 Whether this represents another example of selective protection or is relatable to differences in titers of 0 antibodies was not explored.…”

Study of the protective effects of hyperimmune immunoglobulins G and M against endotoxin in mice and rats

“…To measure the eects of antibodies during endotoxemia, we chose two endotoxin models using chemically characterized LPS [33]. Both these models have been used previously successfully, by ourselves and others [4,19,29,41]. The ®rst used mice sensitized to the lethal eects of LPS by actinomycin D or mice challenged with i.p.-injected bacteria.…”

“…Eects on LPS-induced mortality were estimated using actinomycin D-treated mice as previously described [41]. Brie¯y, serial dilutions of a 1 mg/ml stock suspension of LPS (S and R forms) were prepared in pyrogen-free physiological saline immediately prior to administration.…”

Shared antigens of Porphymmonas gingivalis and Bacteroides forsythus

“…This result was soniewhat enigmatic, since the animals were colonized by several putative periodontal pathogens in addition to P. gingivalis (43). We suspected that, since gram-negative pathogens can express shared antigenic epitopes especially in lipopolysaccharide (12,14,26,36,42) and antibodies to these epitopes can be protective (3,26,36,38), immunization with one species could induce an immune response to antigens of multiple species, thereby accounting in part for the protection observed. We tested this hypothesis using sera from monkeys previously immunized with P. gingivalis (43) and sera from rabbits immunized with either P. gingivalis, B. forsythus or A. actinomycetemcomitans.…”