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Monoclonal immunoglobulin A antibody directed against serotype-specific epitope of Shigella flexneri lipopolysaccharide protects against murine experimental shigellosis.

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Affiliations

  • 1. Unité de Pathogénie Microbienne Moléculaire, U389 Institut National de la Santé et de la Recherche Médicale, Paris, France.
      Authors
    • Phalipon A 1
    (1 author)

The Journal of Experimental Medicine, 01 Sep 1995, 182(3):769-778
https://doi.org/10.1084/jem.182.3.769 PMID: 7544397 PMCID: PMC2192169

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Abstract 

To determine the role of humoral mucosal immune response in protection against shigellosis, we have obtained a monoclonal dimeric immunoglobulin A (IgA) antibody specific for Shigella flexneri serotype 5a lipopolysaccharide (mIgA) and used a murine pulmonary infection model that mimics the lesions occurring in natural intestinal infection. Adult BALB/c mice challenged with 10(7) S. flexneri organisms developed a rapid inflammatory response characterized by polymorphonuclear cell infiltration around and within the bronchi and strong systemic interleukin 6 response. Implantation of hybridoma cells in the back of mice, resulting in the development of a myeloma tumor producing mIgA in the serum and subsequently secretory mIgA in local secretions, or direct intranasal administration of these antibodies, protected the animals against subsequent intranasal challenge with S. flexneri serotype 5a. Absence of histopathological lesion and significant decrease in bacterial load of the lungs and of systemic interleukin 6 response were the three major criteria of protection. This protection was shown to be serotype-specific and dependent on local concentration of mIgA. These data demonstrate that mucosal antibodies directed against a single polysaccharidic surface epitope of Shigella can protect against the disease.

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J Exp Med. 1995 Sep 1; 182(3): 769–778.
PMCID: PMC2192169
PMID: 7544397

Monoclonal immunoglobulin A antibody directed against serotype-specific epitope of Shigella flexneri lipopolysaccharide protects against murine experimental shigellosis

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Abstract

To determine the role of humoral mucosal immune response in protection against shigellosis, we have obtained a monoclonal dimeric immunoglobulin A (IgA) antibody specific for Shigella flexneri serotype 5a lipopolysaccharide (mIgA) and used a murine pulmonary infection model that mimics the lesions occurring in natural intestinal infection. Adult BALB/c mice challenged with 10(7) S. flexneri organisms developed a rapid inflammatory response characterized by polymorphonuclear cell infiltration around and within the bronchi and strong systemic interleukin 6 response. Implantation of hybridoma cells in the back of mice, resulting in the development of a myeloma tumor producing mIgA in the serum and subsequently secretory mIgA in local secretions, or direct intranasal administration of these antibodies, protected the animals against subsequent intranasal challenge with S. flexneri serotype 5a. Absence of histopathological lesion and significant decrease in bacterial load of the lungs and of systemic interleukin 6 response were the three major criteria of protection. This protection was shown to be serotype-specific and dependent on local concentration of mIgA. These data demonstrate that mucosal antibodies directed against a single polysaccharidic surface epitope of Shigella can protect against the disease.

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Selected References

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  • Sansonetti PJ. Molecular mechanisms of cell and tissue invasion by Shigella flexneri. Infect Agents Dis. 1993 Aug;2(4):201–206. [Abstract] [Google Scholar]
  • Mounier J, Vasselon T, Hellio R, Lesourd M, Sansonetti PJ. Shigella flexneri enters human colonic Caco-2 epithelial cells through the basolateral pole. Infect Immun. 1992 Jan;60(1):237–248. [Europe PMC free article] [Abstract] [Google Scholar]
  • Perdomo JJ, Gounon P, Sansonetti PJ. Polymorphonuclear leukocyte transmigration promotes invasion of colonic epithelial monolayer by Shigella flexneri. J Clin Invest. 1994 Feb;93(2):633–643. [Europe PMC free article] [Abstract] [Google Scholar]
  • Wassef JS, Keren DF, Mailloux JL. Role of M cells in initial antigen uptake and in ulcer formation in the rabbit intestinal loop model of shigellosis. Infect Immun. 1989 Mar;57(3):858–863. [Europe PMC free article] [Abstract] [Google Scholar]
  • Perdomo OJ, Cavaillon JM, Huerre M, Ohayon H, Gounon P, Sansonetti PJ. Acute inflammation causes epithelial invasion and mucosal destruction in experimental shigellosis. J Exp Med. 1994 Oct 1;180(4):1307–1319. [Europe PMC free article] [Abstract] [Google Scholar]
  • Zychlinsky A, Prevost MC, Sansonetti PJ. Shigella flexneri induces apoptosis in infected macrophages. Nature. 1992 Jul 9;358(6382):167–169. [Abstract] [Google Scholar]
  • Zychlinsky A, Fitting C, Cavaillon JM, Sansonetti PJ. Interleukin 1 is released by murine macrophages during apoptosis induced by Shigella flexneri. J Clin Invest. 1994 Sep;94(3):1328–1332. [Europe PMC free article] [Abstract] [Google Scholar]
  • Oaks EV, Hale TL, Formal SB. Serum immune response to Shigella protein antigens in rhesus monkeys and humans infected with Shigella spp. Infect Immun. 1986 Jul;53(1):57–63. [Europe PMC free article] [Abstract] [Google Scholar]
  • Dinari G, Hale TL, Austin SW, Formal SB. Local and systemic antibody responses to Shigella infection in rhesus monkeys. J Infect Dis. 1987 May;155(5):1065–1069. [Abstract] [Google Scholar]
  • Oberhelman RA, Kopecko DJ, Salazar-Lindo E, Gotuzzo E, Buysse JM, Venkatesan MM, Yi A, Fernandez-Prada C, Guzman M, León-Barúa R, et al. Prospective study of systemic and mucosal immune responses in dysenteric patients to specific Shigella invasion plasmid antigens and lipopolysaccharides. Infect Immun. 1991 Jul;59(7):2341–2350. [Europe PMC free article] [Abstract] [Google Scholar]
  • Cohen D, Green MS, Block C, Slepon R, Ofek I. Prospective study of the association between serum antibodies to lipopolysaccharide O antigen and the attack rate of shigellosis. J Clin Microbiol. 1991 Feb;29(2):386–389. [Europe PMC free article] [Abstract] [Google Scholar]
  • Mel DM, Arsić BL, Nikolić BD, Radovanić ML. Studies on vaccination against bacillary dysentery. 4. Oral immunization with live monotypic and combined vaccines. Bull World Health Organ. 1968;39(3):375–380. [Europe PMC free article] [Abstract] [Google Scholar]
  • DuPont HL, Hornick RB, Snyder MJ, Libonati JP, Formal SB, Gangarosa EJ. Immunity in shigellosis. II. Protection induced by oral live vaccine or primary infection. J Infect Dis. 1972 Jan;125(1):12–16. [Abstract] [Google Scholar]
  • Formal SB, Kent TH, May HC, Palmer A, Falkow S, LaBrec EH. Protection of monkeys against experimental shigellosis with a living attenuated oral polyvalent dysentery vaccine. J Bacteriol. 1966 Jul;92(1):17–22. [Europe PMC free article] [Abstract] [Google Scholar]
  • Formal SB, Oaks EV, Olsen RE, Wingfield-Eggleston M, Snoy PJ, Cogan JP. Effect of prior infection with virulent Shigella flexneri 2a on the resistance of monkeys to subsequent infection with Shigella sonnei. J Infect Dis. 1991 Sep;164(3):533–537. [Abstract] [Google Scholar]
  • Herrington DA, Van de Verg L, Formal SB, Hale TL, Tall BD, Cryz SJ, Tramont EC, Levine MM. Studies in volunteers to evaluate candidate Shigella vaccines: further experience with a bivalent Salmonella typhi-Shigella sonnei vaccine and protection conferred by previous Shigella sonnei disease. Vaccine. 1990 Aug;8(4):353–357. [Abstract] [Google Scholar]
  • Kärnell A, Stocker BA, Katakura S, Reinholt FP, Lindberg AA. Live oral auxotrophic Shigella flexneri SFL124 vaccine with a deleted aroD gene: characterization and monkey protection studies. Vaccine. 1992;10(6):389–394. [Abstract] [Google Scholar]
  • Cleary TG, Winsor DK, Reich D, Ruiz-Palacios G, Calva JJ. Human milk immunoglobulin A antibodies to Shigella virulence determinants. Infect Immun. 1989 Jun;57(6):1675–1679. [Europe PMC free article] [Abstract] [Google Scholar]
  • Keren DF, Kern SE, Bauer DH, Scott PJ, Porter P. Direct demonstration in intestinal secretions of an IgA memory response to orally administered Shigella flexneri antigens. J Immunol. 1982 Jan;128(1):475–479. [Abstract] [Google Scholar]
  • Tagliabue A, Nencioni L, Villa L, Keren DF, Lowell GH, Boraschi D. Antibody-dependent cell-mediated antibacterial activity of intestinal lymphocytes with secretory IgA. Nature. 1983 Nov 10;306(5939):184–186. [Abstract] [Google Scholar]
  • Weltzin R, Lucia-Jandris P, Michetti P, Fields BN, Kraehenbuhl JP, Neutra MR. Binding and transepithelial transport of immunoglobulins by intestinal M cells: demonstration using monoclonal IgA antibodies against enteric viral proteins. J Cell Biol. 1989 May;108(5):1673–1685. [Europe PMC free article] [Abstract] [Google Scholar]
  • Winner L, 3rd, Mack J, Weltzin R, Mekalanos JJ, Kraehenbuhl JP, Neutra MR. New model for analysis of mucosal immunity: intestinal secretion of specific monoclonal immunoglobulin A from hybridoma tumors protects against Vibrio cholerae infection. Infect Immun. 1991 Mar;59(3):977–982. [Europe PMC free article] [Abstract] [Google Scholar]
  • Meloen RH, Briaire J. A study of the cross-reacting antigens on the intact foot-and-mouth disease virus and its 12S Subunits with antisera against the structural proteins. J Gen Virol. 1980 Nov;51(Pt 1):107–116. [Abstract] [Google Scholar]
  • Renegar KB, Small PA., Jr Passive transfer of local immunity to influenza virus infection by IgA antibody. J Immunol. 1991 Mar 15;146(6):1972–1978. [Abstract] [Google Scholar]
  • Van Snick J, Cayphas S, Vink A, Uyttenhove C, Coulie PG, Rubira MR, Simpson RJ. Purification and NH2-terminal amino acid sequence of a T-cell-derived lymphokine with growth factor activity for B-cell hybridomas. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9679–9683. [Europe PMC free article] [Abstract] [Google Scholar]
  • Michetti P, Mahan MJ, Slauch JM, Mekalanos JJ, Neutra MR. Monoclonal secretory immunoglobulin A protects mice against oral challenge with the invasive pathogen Salmonella typhimurium. Infect Immun. 1992 May;60(5):1786–1792. [Europe PMC free article] [Abstract] [Google Scholar]
  • Neutra MR, Kraehenbuhl JP. The role of transepithelial transport by M cells in microbial invasion and host defense. J Cell Sci Suppl. 1993;17:209–215. [Abstract] [Google Scholar]
  • Takeuchi A, Formal SB, Sprinz H. Exerimental acute colitis in the Rhesus monkey following peroral infection with Shigella flexneri. An electron microscope study. Am J Pathol. 1968 Mar;52(3):503–529. [Europe PMC free article] [Abstract] [Google Scholar]
  • Sansonetti PJ, Arondel J, Fontaine A, d'Hauteville H, Bernardini ML. OmpB (osmo-regulation) and icsA (cell-to-cell spread) mutants of Shigella flexneri: vaccine candidates and probes to study the pathogenesis of shigellosis. Vaccine. 1991 Jun;9(6):416–422. [Abstract] [Google Scholar]
  • Jones KP, Reynolds SP, Capper SJ, Kalinka S, Edwards JH, Davies BH. Measurement of interleukin-6 in bronchoalveolar lavage fluid by radioimmunoassay: differences between patients with interstitial lung disease and control subjects. Clin Exp Immunol. 1991 Jan;83(1):30–34. [Abstract] [Google Scholar]
  • Raqib R, Lindberg AA, Wretlind B, Bardhan PK, Andersson U, Andersson J. Persistence of local cytokine production in shigellosis in acute and convalescent stages. Infect Immun. 1995 Jan;63(1):289–296. [Europe PMC free article] [Abstract] [Google Scholar]
  • Tamura S, Funato H, Hirabayashi Y, Suzuki Y, Nagamine T, Aizawa C, Kurata T. Cross-protection against influenza A virus infection by passively transferred respiratory tract IgA antibodies to different hemagglutinin molecules. Eur J Immunol. 1991 Jun;21(6):1337–1344. [Abstract] [Google Scholar]
  • Lee CK, Weltzin R, Soman G, Georgakopoulos KM, Houle DM, Monath TP. Oral administration of polymeric immunoglobulin A prevents colonization with Vibrio cholerae in neonatal mice. Infect Immun. 1994 Mar;62(3):887–891. [Europe PMC free article] [Abstract] [Google Scholar]
  • Mestecky J, McGhee JR. Immunoglobulin A (IgA): molecular and cellular interactions involved in IgA biosynthesis and immune response. Adv Immunol. 1987;40:153–245. [Abstract] [Google Scholar]
  • Ménard R, Sansonetti P, Parsot C. The secretion of the Shigella flexneri Ipa invasins is activated by epithelial cells and controlled by IpaB and IpaD. EMBO J. 1994 Nov 15;13(22):5293–5302. [Europe PMC free article] [Abstract] [Google Scholar]
  • Taylor HP, Dimmock NJ. Mechanism of neutralization of influenza virus by secretory IgA is different from that of monomeric IgA or IgG. J Exp Med. 1985 Jan 1;161(1):198–209. [Europe PMC free article] [Abstract] [Google Scholar]
  • Mazanec MB, Nedrud JG, Kaetzel CS, Lamm ME. A three-tiered view of the role of IgA in mucosal defense. Immunol Today. 1993 Sep;14(9):430–435. [Abstract] [Google Scholar]
  • Michetti P, Porta N, Mahan MJ, Slauch JM, Mekalanos JJ, Blum AL, Kraehenbuhl JP, Neutra MR. Monoclonal immunoglobulin A prevents adherence and invasion of polarized epithelial cell monolayers by Salmonella typhimurium. Gastroenterology. 1994 Oct;107(4):915–923. [Abstract] [Google Scholar]
  • Apter FM, Lencer WI, Finkelstein RA, Mekalanos JJ, Neutra MR. Monoclonal immunoglobulin A antibodies directed against cholera toxin prevent the toxin-induced chloride secretory response and block toxin binding to intestinal epithelial cells in vitro. Infect Immun. 1993 Dec;61(12):5271–5278. [Europe PMC free article] [Abstract] [Google Scholar]
  • Shen L. Receptors for IgA on phagocytic cells. Immunol Res. 1992;11(3-4):273–282. [Abstract] [Google Scholar]
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