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Prevention and therapy of experimental Escherichia coli infection with monoclonal antibody
Abstract:
Mouse hybridoma antibody of immunoglobulin class M prepared with live group B meningococci was evaluated for its ability to protect against and treat Escherichia coli infections in a newborn-rat model. In these studies, antibody was administered intraperitoneally and bacteria were administered subcutaneously to avoid introducing the antibody and bacteria to the same site. The activity of this hybridoma antibody was specific; the antibody provided protection against the K-1 strain, but not against the K-92 strain. In addition, the amount of the antibody required for protection was dependent upon the size of bacterial challenge. With an increase of the bacterial inocula from the 100% lethal dose to 10 times the 100% lethal dose there was a threefold increase in the amount of the antibody required for 50% protection. Similarly, therapeutic efficacy of the antibody was also dependent upon the magnitude of bacteremia before therapy. The antibody successfully cleared the bacteremia only when the pretherapy bacterial counts in blood were less than 10(4) CFU/ml. These findings suggest that the monoclonal immunoglobulin M antibody against the capsular polysaccharide of the group B meningococcus may be useful in the prevention and treatment of K-1 E. coli infections.
Insights
This study shows a mouse monoclonal antibody against group B meningococci can protect and treat K-1 Escherichia coli infections in newborn rats. Efficacy depends on bacterial challenge size and pre-therapy blood counts.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Group B Streptococcus infections pose a significant threat, particularly in neonates.
- Escherichia coli, specifically the K-1 strain, is a common cause of neonatal meningitis and sepsis.
- Developing effective therapeutic strategies against these pathogens is crucial.
Purpose of the Study:
- To evaluate the protective and therapeutic potential of a mouse hybridoma antibody (immunoglobulin M) against Escherichia coli K-1 infections.
- To determine the specificity and dose-dependency of the antibody's efficacy in a newborn rat model.
Main Methods:
- A mouse hybridoma antibody of immunoglobulin class M was prepared using live group B meningococci.
- The antibody was administered intraperitoneally, and Escherichia coli (K-1 and K-92 strains) were administered subcutaneously in newborn rats.
- Protection and treatment efficacy were assessed based on bacterial challenge size and pre-therapy bacteremia levels.
Main Results:
- The hybridoma antibody demonstrated specific activity, protecting against the K-1 strain but not the K-92 strain of Escherichia coli.
- Antibody efficacy was dose-dependent, with higher bacterial challenges requiring threefold more antibody for 50% protection.
- Therapeutic success in clearing bacteremia was achieved only when pre-therapy bacterial counts were below 10(4) CFU/ml.
Conclusions:
- Monoclonal immunoglobulin M antibody against the capsular polysaccharide of group B meningococcus shows promise for preventing and treating K-1 Escherichia coli infections.
- The findings highlight the importance of bacterial load and strain specificity in antibody-mediated protection and therapy.
- This antibody could be a valuable tool in combating specific neonatal bacterial infections.