Antiendotoxin Antibodies: A Dead End? (1994)

Editorials1 July 1994Antiendotoxin Antibodies: A Dead End?Alan S. Cross, MDAlan S. Cross, MDWalter Reed Army Institute of Research, Washington, D.C. 20307-5100.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-121-1-199407010-00011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail During the last 30 years, the increased recognition of gram-negative bacillary sepsis and its high mortality (30% to 50%) led investigators to seek strategies to supplement conventional antibiotic treatment. During the 1960s, the structural features of gram-negative bacterial lipopolysaccharide, or endotoxin, were identified: a common, toxic lipid A moiety; an inner-core sugar region; and an antigenically distinct, O polysaccharide side chain. Experimental studies by Chedid, Braude, McCabe, and colleagues [1-3] suggested that antibodies directed toward epitopes in the inner-core sugar region of the lipopolysaccharide (which are widely shared by gram-negative bacilli) may be broadly protective.As a result of these ...References1. Chedid L, Parant M, Parant F, Boyer F. A proposed mechanism for natural immunity to enterobacterial pathogens. J Immunol. 1968; 100:292-306. Google Scholar2. Braude AI, Ziegler EJ, McCutchan JA, Douglas H. Immunization against nosocomial infection. Am J Med. 1981; 70:463-6. Google Scholar3. McCabe WR, Greely A. Immunization with R mutants of Salmonella minnesota. I. Protection against challenge with heterologous gram-negative bacilli. J Immunol. 1972; 108:601-10. Google Scholar4. Ziegler EJ, McCutchan JA, Fierer J, Glauser MP, Sadoff JC, Douglas H, et al. Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli. N Engl J Med. 1982; 307:1225-30. Google Scholar5. Ziegler EJ, Fisher CJ Jr, Sprung CL, Straube RC, Sadoff JC, Foulke GE, et al. Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. The HA-1A Sepsis Study Group. N Engl J Med. 1991; 324:429-36. Google Scholar6. Greenman RL, Schein RMH, Martin MA, Wenzel RP, MacIntyre NR, Emmanuel G, et al. A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. The XOMA Sepsis Study Group. JAMA. 1991; 266:1097-102. Google Scholar7. Warren HS, Danner RL, Munford RS. Anti-endotoxin monoclonal antibodies. N Engl J Med. 1992; 326:1153-7. Google Scholar8. McCloskey RV, Straube RC, Sanders C, Smith SM, Smith CR, The CHESS Trial Study Group. Treatment of septic shock with human monoclonal antibody HA-1A: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1994; 120:1-5. Google Scholar9. Wenzel R, Bone R, Fein A, Quenzer R, Schentag J, Gorelick KJ, et al. Results of a second double-blind, randomized, controlled trial of antiendotoxin antibody E5 in gram-negative sepsis. Program and Abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago; 1991:294. Google Scholar10. Baumgartner JD. Immunotherapy with antibodies to core lipopolysaccharide: a critical appraisal. Infect Dis Clin North Am. 1991; 5:915-27. Google Scholar11. Zinner SH, McCabe WR. Effects of IgM and IgG antibody in patients with bacteremia due to gram-negative bacilli. J Infect Dis. 1976; 133:37-45. Google Scholar12. Pollack M, Huang AI, Prescott RK, Young LS, Hunter KW, Cruess DF, et al. Enhanced survival in Pseudomonas aeruginosa septicemia associated with high levels of circulating antibody to Escherichia coli endotoxin core. J Clin Invest. 1983; 72:1874-81. Google Scholar13. McCabe WR, DeMaria A Jr, Berberich H, Johns MA. Immunization with rough mutants of Salmonella minnesota: protective activity of IgM and IgG antibody to the R595 (Re chemotype) mutant. J Infect Dis. 1988; 158:291-300. Google Scholar14. Bhattacharjee AK, Opal SM, Drabick JJ, Collins H, Taylor R, Cotton A, et al. Affinity purified E. coli J5 LPS-specific IgG protects neutropenic rats against gram-negative bacterial sepsis. J Infect Dis. 1994; 170:(In press). Google Scholar15. Calandra T, Glauser MP, Schellekens J, Verhoef J. Treatment of gram-negative septic shock with human IgG antibody to Escherichia coli J5: a prospective, double-blind, randomized trial. J Infect Dis. 1988; 158:312-9. Google Scholar16. J5 Study Group. Treatment of severe infectious purpura in children with human plasma from donors immunized with Escherichia coli J5: a prospective double-blind study. J Infect Dis. 1992; 165:695-701. Google Scholar17. Havell EA, Moldawer LL, Helfgott D, Kilian PL, Sehgal PB. Type 1 interleukin-1 receptor blockade exacerbates murine listeriosis. J Immunol. 1992; 148:1486-91. Google Scholar18. Bennett IL Jr. Approaches to the mechanisms of endotoxin action. In: Braun W, Landy M, eds. Bacterial Endotoxins: Proceedings of a Symposium Held at the Institute of Microbiology of Rutgers, the State University. New Brunswick: Institute of Microbiology, Rutgers, the State University; 1964: xiii-vi. Google Scholar Author, Article, and Disclosure InformationAuthors: Alan S. Cross, MDAffiliations: Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.Corresponding Author: Alan S. Cross, MD, Department of Bacterial Diseases, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoTreatment of Septic Shock with Human Monoclonal Antibody HA-1A Richard V. McCloskey , Richard C. Straube , Corazon Sanders , Susan M. Smith , Craig R. Smith , and Metrics Cited byOuter membrane vesicles as molecular biomarkers for Gram-negative sepsis: Taking advantage of nature’s perfect packagesThe FutureVaccines Against Escherichia coliEngineering Antibodies for the Treatment of Infectious DiseasesDevelopment trends for human monoclonal antibody therapeuticsAntibodies for Sepsis: Some Lessons LearntRandomized Controlled Trials in SepsisPassive Immunization to Outer Membrane Proteins MLP and PAL Does Not Protect Mice from SepsisAnti-endotoxin antibodiesAnti-endotoxin antibodiesProspects for a Vaccine to Prevent Bacterial SepsisAntibodies for Sepsis: Some Lessons LearntAntibody Therapy for Sepsis: Some Lessons LearnedThe role of polar and facial amphipathic character in determining lipopolysaccharide-binding properties in synthetic cationic peptidesBinding to and Opsonophagocytic Activity of O-Antigen-Specific Monoclonal Antibodies against Encapsulated and Nonencapsulated Klebsiella pneumoniae Serotype O1 StrainsOuter Membrane Protein A, Peptidoglycan-Associated Lipoprotein, and Murein Lipoprotein Are Released by Escherichia coli Bacteria into SerumA Double-Blind Placebo-Controlled Study of an Infusion of Lexipafant (Platelet-Activating Factor Receptor Antagonist) in Patients with Severe SepsisANTIENDOTOXIN STRATEGIESLipopolyamines: Novel Antiendotoxin Compounds That Reduce Mortality in Experimental Sepsis Caused by Gram-Negative BacteriaConfirmatory platelet-activating factor receptor antagonist trial in patients with severe Gram-negative bacterial sepsisIs Reduction in Mortality in Intensive Care Just Another Holy Grail?Confirmatory interleukin-1 receptor antagonist trial in severe sepsisSeptic Shock in Bacteremic Patients: Risk Factors, Features and PrognosisStreptococcal toxic shock syndrome from a puncture wound to the footPaper one: Resource allocation in cancer medicine: Invest where the benefits are clearEndotoxin-Based Molecular Strategies for the Prevention and Treatment of Gram-Negative Sepsis and Septic ShockAdult Respiratory Distress Syndrome: A Radical PerspectiveUse of Predicted Risk of Mortality to evaluate the efficacy of anticytokine therapy in sepsisReview: Bacterial endotoxin and the human monoclonal antibody HA-IA: specificity, potential mechanisms of action, and limits to its effectivenessADJUNCTS TO ANTIBACTERIAL THERAPYA second large controlled clinical study of E5, a monoclonal antibody to endotoxinLessons learned from clinical trials of sepsisShould morbidity replace mortality as an endpoint for clinical trials in intensive care?New strategies for combatting sepsis: the magic bullets missed the mark…but the search continuesClinical Trials of Novel Therapeutic Agents: Why did they fail? 1 July 1994Volume 121, Issue 1Page: 58-60KeywordsAntibodiesBacteremiaClinical trialsCytokinesEndotoxinsMonoclonal antibodiesMortalitySafety studiesSepsisShock ePublished: 15 August 2000 Issue Published: 1 July 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. 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