Conclusions
The results obtained by numerous investigators reveal the ability of antibodies to cross-reactive LPS antigens to protect against infections caused by various gram-negative pathogens and their endotoxins. Based upon experimental and clinical experience, one could postulate that these antibodies are a promising approach for the prophylaxis and therapy of sepsis. The recognition of high-risk patients would allow early start of combined therapy with appropriate immune preparations and antibiotics, which along with life-supporting measures (corticosteroids, electrolyte and nutrition infusions, etc.), would be a useful tool in the treatment of gram-negative sepsis and endotoxin shock.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Maki, D. G. Nosocomial bacteremia. An epidemiologic overview. In:Dixon, R. E. (ed.): Nosocomial infections. Yorke Medical Books, New York 1981, pp. 183–196.
Duma, R. J. Gram-negative bacillary infections. Pathogenetic and pathophysiologic correlations. Am. J. Med. 78 (Suppl. 6A) (1985) 154–164.
Warren, H. S., Chedid, L. A. Strategies for the treatment of endotoxemia: significance of the acute-phase response. Rev. Infect. Dis. 9 (Suppl. 5) (1987) 630–638.
Baumgartner, J. D., Glauser, M. P., McCutchan, J. A., Ziegler, E. J., Van Malle, G., Klaubner, M. R., Vogt, M., Muehlen, E., Luethy, R., Chiolero, R., Geroulanos, S. Prevention of gram-negative shock and death in surgical patients by antibody to endotoxin core glycolipid. Lancet ii (1985) 59–63.
Marget, W., Mar, P. J., Jaspers, L., Possinger, K., Haslberg, H. Preliminary study on administration of high-titer lipid A antibody serum in sepsis and septic shock patients. Infection 13 (1985) 120–124.
Ziegler, E. J., McCutchan, J. A., Fierer, J., Glauser, M. P., Sadoff, J., Douglas, H., Braude, A. I. Treatment of gram-negative bacteremia and shock with human antiserum to a mutant ofEscherichia coli. N. Engl. J. Med. 307 (1982) 1225–1230.
Westphal, O., Luderitz, O., Galanos, C., Mayer, H., Rietschel, E.: The story of bacterial endotoxin. In:Chedid, L., Hadden, J. W., Dukor, P., Willoghby, D. (eds.): Advanced immunopharmacology. 3 (1986) pp. 13–34.
Lüderitz, O., Staub, A. M., Westphal, O. Immunochemistry of O and R antigens ofSalmonella and relatedEnterobacteriaceae. Bacteriol. Rev. 30 (1966) 192–255.
Radziejewska-Lebrecht, J., Bhat, R., Brade, J., Mayer, H. Structural studies on the core and lipid A region of a 4-amino-L-arabinoselacking Rc type mutant ofProteus mirabilis. Eur. J. Biochem. 172 (1988) 535–541.
Helander, I. M., Vaara, M., Sukopolvi, S., Rhen, M., Saarela, S., Zahringer, V., Makela, P. H. rfaP mutants ofSalmonella typhimurium. Eur. J. Biochem. 185 (1989) 541–546.
Radziejewska-Lebrecht, J., Mayer, H. The core region ofProteus mirabilis R 110/1959 lipopolysaccharide. Eur. J. Biochem. 183 (1989) 573–581.
Rowe, P. S. N., Meadow, P. M. Structure of the core oligosaccharide from the lipopolysaccharide ofPseudomonas aeruginosa PAC 1R and its defective mutants. Eur. J. Biochem. 132 (1983) 329–337.
Pollack, M., Chia, J. K. S., Koles, N. L., Miller, M., Guelde, G. Specificity and cross-reactivity of monoclonal antibodies reactive with the core and lipid A regions of bacterial lipopolysaccharide. J. Infect. Dis. 159 (1989) 168–188.
de Jongh-Leuvenink, J., Schellekens, J., Verhoef, J. Characterization of anti-core glycolipid monoclonal antibodies with chemically defined lipopolysaccharides. Infect. Immun. 58 (1990) 421–426.
Galanos, C., Lüderitz, O., Westphal, O. Preparation and properties of antisera against the lipid A component of bacterial lipopolysaccharides. Eur. J. Biochem. 24 (1971) 116–122.
Galanos, C., Freudenberg, M. A., Jay, F., Nerkar, D., Veleva, K., Brade, H., Strittmatter, W. Immunogenic properties of lipid A. Rev. Infect. Dis. 6 (1984) 546–552.
Braude, A. I., Douglas, H., Davis, C. E. Treatment and prevention of intravascular coagulation with antiserum to endotoxin. J. Infect. Dis. 128 (Suppl.) (1973) 157–164.
Tate, W. J., Douglas, H., Braude, A. I. Protection against lethality ofEscherichia coli endotoxin with “O” antiserum. Ann. NY Acad. Sci. 133 (1966) 746–762.
Nelles, M. J., Niswander, C. A. Mouse monoclonal antibodies reactive with J5 lipopolysaccharide exhibit extensive serological cross-reactivity with a variety of gram-negative bacteria. Infect. Immun. 46 (1984) 677–681.
Elkins, K., Metcalf, E. S. Binding activity of a murine anti-lipid A monoclonal antibody. Infect. Immun. 48 (1985) 597–600.
Gigliotti, F., Shenep, J. L. Failure of monoclonal antibodies to core glycolipid to bind intact smooth strains ofEscherichia coli. J. Infect. Dis. 151 (1985) 1005–1011.
de Jongh-Leuvenink, J., Vreede, R. W., Marcelis, J. H., de Vos, M., Verhoef, J. Detection of antibodies against lipopolysaccharides ofEscherichia coli andSalmonella R and S strains by immunoblotting. Infect. Immun. 50 (1985) 716–720.
Siber, G. R., Kania, S. A., Warren, H. S. Cross-reactivity of rabbit antibodies to lipopolysaccharides ofEscherichia coli J5 and other gram-negative bacteria. J. Infect. Dis. 152 (1985) 954–963.
Schwartzer, T. A., Alcid, D. V., Numsuwan, V., Gocke, D. J. Immunochemical specificity of human antibodies to lipopolysaccharide from J5 R mutant ofE. coli O111:B4. J. Infect. Dis. 159 (1989) 35–42.
Bogard, W. C., Dunn, D. L., Abernethy, K., Killgarif, C., Kung, P. C. Isolation and characterisation of murine monoclonal antibodies specific for gram-negative bacterial lipopolysaccharide: association of cross-genus reactivity with lipid A specificity. Infect. Immun. 55 (1987) 899–908.
Barclay, G. R., Scott, B. B. Serological relationship betweenEscherichia coli andSalmonella smooth- and rough-mutant lipopolysaccharides as revealed by ELISA for human immunoglobulin G anti-endotoxin antibodies. Infect. Immun. 55 (1987) 2706–2714.
Schwartzer, T. A., Alcid, D. V., Numsuwan, V., Gocke, D. J. Immunochemical specificity of cross-reactive antibodies to lipopolysaccharides fromEscherichia coli J5. J. Infect. Dis. 155 (1987) 1076–1081.
Bruins, S. C., Stumacher, R., Johns, M. A., McCabe, W. R. Immunization with R mutants ofSalmonella minnesota. III. Comparison of the protective effect of immunization with lipid A and the Re mutant. Infect. Immun. 17 (1977) 16–20.
Sakulramrung, R., Dominique, G. J. Cross-reactive immunoprotective antibodies toEscherichia coli O111 rough mutant J5. J. Infect. Dis. 151 (1985) 995–1004.
Teng, N. N. H., Kaplan, H. S., Hebert, J. M., Moore, C., Douglas, H., Winderlich, A., Braude, A. I. Protection against gram-negative bacteremia and endotoxemia with human monoclonal IgM antibodies. Proc. Natl. Acad. Sci. USA 82 (1985) 1790–1794.
Dunn, D. L., Ferguson, R. M. Immunotherapy of gram-negative bacterial sepsis: enhanced survival in a guinea pig model by use of rabbit antiserum toEscherichia coli J5. Surgery 92 (1982) 212–219.
Mutharia, L. M., Crockford, G., Bogard, W. C., Hancock, R. E. W. Monoclonal antibodies specific forEscherichia coli J5 lipopolysaccharide: cross reaction with other gram-negative bacterial species. Infect. Immun. 45 (1984) 631–636.
Girard, R., Chaly, R. Inhibition of lipopolysaccharide mitogenicity with characterized anti-lipid A monoclonal antibodies. Immunology 56 (1985) 481–489.
Pollack, M., Raubitschek, A. A., Larrick, J. W. Human monoclonal antibodies that recognize conserved epitopes in the core-lipid A region of lipopolysaccharide. J. Clin. Invest. 79 (1987) 1424–1430.
Coughlin, R. T., Bogard, W. C. Immunoprotective murine monoclonal antibodies specific for the outer-core polysaccharide and for the O-antigen ofEscherichia coli O111:B4 lipopolysaccharide (LPS). J. Immunol. 139 (1987) 557–561.
McCabe, W. R., Bruins, S. C., Craven, D. E., Johns, M. A. Cross-reactive antigens: their potential for immunization-induced immunity to gram- negative bacteria. J. Infect. Dis. 136 (Suppl.) (1977) 161–166.
Ward, D. C., Michalek, S. M., McGhee, J. R. Monoclonal antibodies toSalmonella lipopolysaccharide: functional analysis of anti-lipid A antibodies. Clin. Exp. Immunol. 72 (1988) 157–163.
Tsang, R. W., Chan, K. H., Chan, P. Y., Wan, K. C., Ng, M. H., Schlecht, S. A murine monoclonal antibody specific for outer core oligosaccharide ofSalmonella lipopolysaccharide. Infect. Immun. 55 (1987) 211–216.
Aydintug, M. K., Inzana, T. J., Letonja, T., Davis, W. C., Corbeil, L. B. Cross-reactivity of monoclonal antibodies toEscherichia coli J5 with heterologous gram-negative bacteria and extracted lipopolysaccharides. J. Infect. Dis. 160 (1989) 846–857.
Appelmelk, B. J., Verwej-Van Vugt, A. M. J. J., Maaskant, J. J., Schouten, W. F., DeJonge, A. J. R., Thijs, L. G., MacLaren, D. M. Production and characterization of mouse monoclonal antibodies reacting with the lipopolysaccharide core region of gram-negative bacilli. J. Med. Microbiol. 26 (1988) 107–114.
Nys, M., Damas, P., Damas, F., Joassin, L., Demonty, J. A direct ELISA for antibodies to enterobacterial Re core glycolipid and lipid A. Results in healthy subjects and in patients infected by gram-negative bacteria. Med. Microbiol. Immunol. 176 (1987) 257–271.
Dunn, D. L., Bogard, W. C., Cerra, F. B. Efficacy of type-specific and cross-reactive murine monoclonal antibodies directed against endotoxin during experimental sepsis. Surgery 98 (1985) 283–289.
Appelmelk, B., Gruteke, P., Van Vught, M. V., Maaskant, J., Thijs, B., MacLaren, D. Measurement in human sera of antibodies to lipopolysaccharide ofEscherichia coli J5. Microb. Pathogen. 2 (1987) 391–393.
Fenwick, B. W., Cullor, J. S., Osburn, B. I., Olander, H. J. Mechanisms involved in protection provided by immunization against core lipopolysaccharides ofE. coli J5 from lethalHaemophilus pleuropneumoniae infections in swine. Infect. Immun. 53 (1986) 298–304.
Pollack, M., Huang, A. I., Prescott, R. K., Young, L. S., Hunter, K. W., Cruess, D. F., Tsai, C. Enhanced survival inPseudomonas aeruginosa septicemia associated with high levels of circulating antibody toEscherichia coli endotoxin core. J. Clin. Invest. 72 (1983) 1874–1881.
Fox, E. S. Processing of bacterial endotoxins by rat liver Kupffer cells. In:Wisse, E., Knock, D. L., Decker, K. (eds.): Cells of the hepatic sinusoid. Volume 2. Kupffer Cell Foundation, Rijswijk, The Netherlands 1989, pp. 305–308.
Freudenberg, M. A., Kleine, B., Galanos, C. Fate of lipopolysaccharide in rats: evidence for chemical alteration in the molecule. Rev. Infect. Dis. 6 (1984) 483–487.
Kim, Y. B., Watson, D. W. Role of antibodies in reaction to gramnegative bacterial endotoxins. Ann. NY Acad. Sci. 133 (1966) 727–745.
Rietschel, E. Th., Galanos, C. Lipid A antiserum-mediated protection against lipopolysaccharide- and lipid A-induced fever and skin necrosis. Infect. Immun. 15 (1977) 34–49.
Rioux-Darrieulat, F., Parant, M., Chedid, L. Prevention of endotoxin-induced abortion by treatment of mice with antisera. J. Infect. Dis. 137 (1978) 7–13.
Feeley, T. W., Minty, B. D., Scudder, C. M., Jones, J. G., Royston, D., Teng, N. N. H. The effect of human antiendotoxin monoclonal antibodies on endotoxin-induced lung injury in the rat. Am. Rev. Resp. Dis. 135 (1987) 665–670.
Young, L. S. Monoclonal antibodies: technology and application to gram-negative infections. Infection 12 (1984) 303–308.
Marget, W. Lipoid A-Antikörpertiter bei Menschen. Infection 15 (Suppl. 2) (1987) 85–89.
Jaspers, L., Marget, W., Mar, P. J., Hoffmann, K., Langecker, P., Ruckdeschel, G., Obermeier, A., Kastenbauer, E. Antikörper gegen Lipoid A in der Behandlung des septischen Schocks. Infection 15 (Suppl. 2) (1987) 89–95.
Chedid, L., Parant, M., Parant, F., Boyer, F. A proposed mechanism for natural immunity to enterobacterial pathogens. J. Immunol. 100 (1968) 292–301.
McCabe, W. R., De Maria, A., Berberich, H., Johns, M. A. Immunization with rough mutants ofSalmonella minnesota: protective activity of IgM and IgG antibody to the R595 (Re chemotype) mutant. J. Infect. Dis. 158 (1988) 291–300.
De Maria, A., Johns, M. A., Berberich, H., McCabe, W. R. Immunization with rough mutants ofSalmonella minnesota: initial studies in human subjects. J. Infect. Dis. 158 (1988) 301–311.
Nys, M., Cloes, J. M., Demonty, J., Joassin, L. Protective effects of polyclonal antisera and monoclonal antibodies active toSalmonella minnesota Re 595 lipopolysaccharide during experimental endotoxemia. J. Infect. Dis. 162 (1990) 1087–1096.
Yoshida, M., Kudoh, K., Hirata, M. Neutralizing effects of anti-Salmonella Re antibody on endotoxic bone marrow reactions and induction of procoagulant activity. In:Agarwal, M. (ed.): Immunopharmacology of endotoxicosis. Walter de Gyuter, Berlin 1984, pp. 77–93.
Konstantinov, G., Eskenazy, M., Ivanova, R., Vassileva, J., Naumova, F., Tekelieva, R., Strachilov, D. Passive protection against heterologous gram-negative bacteria mediated by antiserum to epimeraseless Re mutant ofSalmonella minnesota. Ann. Inst. Pasteur 133 (1982) 71–76.
Marks, M. I., Ziegler, E. J., Douglas, H., Corbeil, L. B., Braude, A. I. Induction of immunity against lethalHaemophilus influenzae type b infection byEscherichia coli core lipopolysaccharide. J. Clin. Invest. 69 (1982) 742–749.
Warren, H. W., Novitsky, T. J., Bucklin, A., Kania, S. A., Siber, G. R. Endotoxin neutralization with rabbit antisera toE. coli J5 and other gram-negative bacteria. Infect. Immun. 55 (1987) 1668–1673.
Calandra, T., Glauser, M. P., Schellekens, J., Verhoef, J., andthe Swiss-Dutch J5 Immunoglobulin Study Group Treatment of gram-negative septic shock with human IgG antibody toE. coli J5: a prospective, double-blind randomized trial. J. Infect. Dis. 158 (1988) 312–319.
Cohen, J., Hashimi, S. A., Apperley, J. F., Moore, R., Jones, L., Aber, V. Antibody titers to a R-mutant strain ofE. coli in patients undergoing allogeneic bone marrow transplantation. Lancet i (1987) 8–11.
Greisman, S. E., DuBuy, J. B., Woodward, C. L. Experimental gramnegative bacterial sepsis: reevaluation of the ability of rough mutant antisera to protect mice. Proc. Soc. Exp. Biol. Med. 158 (1978) 482–490.
Greisman, S. E., Johnston, C. A. Failure of antisera to J5 and R595 rough mutants to reduce endotoxic lethality. J. Infect. Dis. 157 (1988) 54–64.
Fomsgaard, A. Antibodies to lipopolysaccharides: some diagnostic and protective aspects. APMIS 98 (Suppl. 18) (1990) 5–38.
Trautmann, M., Hahn, H. Antiserum againstEscherichia coli J5: a reevaluation of itsin vitro andin vivo activity against heterologous gram-negative bacteria. Infection 13 (1985) 140–145.
Morris, D. D., Witlock, R. H., Corbeil, L. B. Endotoxemia in horses: protection provided by antiserum to core lipopolysaccharide. Am. J. Vet. Res. 47 (1986) 544–550.
Johns, M. A., Skehil, A., McCabe, W. R. Immunization with rough mutants ofSalmonella minnesota: IV. Protection by antisera to O and rough antigens endotoxin. J. Infect. Dis. 147 (1983) 57–67.
Ziegler, E. J., McCutchan, J. A., Douglas, H., Braude, A. I. Prevention of lethalPseudomonas bacteremia with epimerase-deficientEscherichia coli antisera. Trans. Assoc. Am. Physicians 88 (1975) 101–108.
Schiller, N. L. Characterization of the susceptibility ofPseudomonas aeruginosa to complement mediated-killing: role of antibodies to the rough lipopolysaccharide on serum-sensitive strains. Infect. Immun. 56 (1988) 632–639.
Mattsby-Baltzer, I., Alving, C. R. Antibodies to lipid A: occurrence in humans. Rev. Infect. Dis. 6 (1984) 553–557.
Marget, W., Weiss, M., Ruhland, B. Lipid A antibody determination using ELISA in patients at a children's hospital: a preliminary report. Infection 11 (1983) 82–84.
Westenfelder, M., Galanos, C., Madson, P. O., Marget, W. Pathological activity of lipid A: experimental studies in relation to chronic pyelonephritis. In:Schlessinger, D. (ed.): Microbiology. American Society for Microbiology, Washington D.C. 1977, pp. 277–279.
McCabe, W. R., Kreger, B. E., Johns, M. A. Type-specific and cross-reactive antibodies in gram-negative bacteremia. N. Engl. J. Med. 287 (1972) 261–267.
Cross, A. S., Sidberry, H., Sadoff, J. C. The human antibody response during natural bacteremic infection with gram-negative bacilli against lipopolysaccharide core determinants. J. Infect. Dis. 160 (1989) 225–236.
Schellekens, J. F. P., Benne, C. A., De Zeeuw, G. R., Rosenberg-Arska, M., Verhoef, J. Naturally occurring IgG and IgM antibodies to gram-negative bacteria and lipopolysaccharides in human sera. Serodiagn. Immunother. Infect. Dis. 2 (1988) 433–444.
Stoll, C., Schedel, I., Peest, D. Serum antibodies against common antigens of bacterial lipopolysaccharides in healthy adults and in patients with multiple myeloma. Infection 13 (1985) 115–119.
Schedel, I., Stoll, C., Nentwig, B. Serum antibodies against common antigens of bacterial lipopolysaccharide — a useful indicator for clinically relevant secondary immunodeficiency. Topics Aging Res. Europe 5 (1985) 131–135.
Pennington, J. E., Pier, G. B. Pseudomonas aeruginosa-Immunoglobin bei experimenteller Pneumonie. Infection 15 (Suppl. 2) (1987) 47–51.
Verhoef, J. Antibodies against endotoxin. In:Geraci, E., Verhoef, J., Filadoro, F., Renzini, G., Goldstein, A. (eds.): Microbiological, chemotherapeutical and immunological problems in high risk patients. Serano Symp. Publ., Volume 61. Raven Press, New York 1989, pp. 1–7.
Young, L. S.: Functional activity of monoclonal antibodies against lipopolysaccharide (LPS) antigens of gram-negative bacilli. Clin. Res. 32 (1984) Abstract 518 A.
Collins, M. S., Hector, R. F., Roby, R. E., Edwards, A. A., Ladehoff, D. K., Dorsey, J. H. Prophylaxe gramnegativer und grampositiver Infektionen mit drei intravenösen Immunglobulin-Präparaten und Therapie der experimentellen polymikrobiellen Verbrennungssepsis mit intravenösemPseudomonas-Immunoglobulin G und Ciprofloxacin im Tiermodell. Infection 15 (Suppl. 2) (1987) 51–60.
Veerde, R. W., Marcelis, J. H., Verhoef, J. Antibodies against rough mutants ofEscherichia coli andSalmonella strains are opsonic only in the presence of complement. Infect. Immun. 52 (1986) 892–896.
Chong, K. T., Huston, M. Implication of endotoxin contamination in the evaluation of antibodies to lipopolysaccharides in murine model of gram-negative sepsis. J. Infect. Dis. 156 (1987) 713–719.
Ziegler, E. J. Protective antibody to endotoxin core: the emperor's new clothes? J. Infect. Dis. 158 (1988) 286–290.
Baumgartner, J. D., O'Brien, T. X., Kirkland, T. N., Glauser, M. P., Ziegler, E. J. Demonstration of cross-reactive antibodies to smooth gram-negative bacteria in antiserum toEscherichia coli J5. J. Infect. Dis. 156 (1987) 136–147.
Jirillo, E., Kiyona, H., Michalek, S. M., Fumarola, D., McGhee, J. R. Murine immune response to theSalmonella lipopolysaccharide regions. In:Agarwal, M. K. (ed.): Immunopharmacology of endotoxicosis. Walter de Guyter and Co., New York 1984, pp. 93–106.
Schlecht, S., Westphal, O. Protective role ofSalmonella R-mutants inSalmonella infection in mice. Zentralbl. Bact. Hyg. I. Abt. Orig. 245 (1979) 71–88.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mitov, I.G., Terziiski, D.G. Immunoprophylaxis and immunotherapy of gram-negative sepsis and shock with antibodies to core glycolipids and lipid a of bacterial lipopolysaccharides. Infection 19, 383–390 (1991). https://doi.org/10.1007/BF01726444
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01726444