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. 1995 Jun;63(6):2382–2386. doi: 10.1128/iai.63.6.2382-2386.1995

Intransal or intragastric immunization with proteosome-Shigella lipopolysaccharide vaccines protects against lethal pneumonia in a murine model of Shigella infection.

C P Mallett 1, T L Hale 1, R W Kaminski 1, T Larsen 1, N Orr 1, D Cohen 1, G H Lowell 1
PMCID: PMC173317  PMID: 7768627

Abstract

Mice immunized intransally or intragastrically with proteosome vaccines containing either Shigella sonnei or S. flexneri 2a lipopolysaccharide were protected against lethal pneumonia caused by homologous organisms in an experimental murine intranasal challenge model of Shigella infection. Histopathological analysis demonstrated that immunization also protected against the progressive lesions resulting from invasion of the pulmonary mucosa by S. sonnei. These data show that mucosal proteosome-lipopolysaccharide vaccines can protect against lethal bacterial pneumonia and indicate that such vaccines are promising candidates for protection against intestinal shigellosis.

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Selected References

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  1. Black R. E., Levine M. M., Clements M. L., Young C. R., Svennerholm A. M., Holmgren J. Protective efficacy in humans of killed whole-vibrio oral cholera vaccine with and without the B subunit of cholera toxin. Infect Immun. 1987 May;55(5):1116–1120. doi: 10.1128/iai.55.5.1116-1120.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chelen C. J., Fang Y., Freeman G. J., Secrist H., Marshall J. D., Hwang P. T., Frankel L. R., DeKruyff R. H., Umetsu D. T. Human alveolar macrophages present antigen ineffectively due to defective expression of B7 costimulatory cell surface molecules. J Clin Invest. 1995 Mar;95(3):1415–1421. doi: 10.1172/JCI117796. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chen K. S., Burlington D. B., Quinnan G. V., Jr Active synthesis of hemagglutinin-specific immunoglobulin A by lung cells of mice that were immunized intragastrically with inactivated influenza virus vaccine. J Virol. 1987 Jul;61(7):2150–2154. doi: 10.1128/jvi.61.7.2150-2154.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cohen D., Green M. S., Block C., Rouach T., Ofek I. Serum antibodies to lipopolysaccharide and natural immunity to shigellosis in an Israeli military population. J Infect Dis. 1988 May;157(5):1068–1071. doi: 10.1093/infdis/157.5.1068. [DOI] [PubMed] [Google Scholar]
  5. Cohen D., Green M. S., 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. doi: 10.1128/jcm.29.2.386-389.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Eldridge J. H., Gilley R. M., Staas J. K., Moldoveanu Z., Meulbroek J. A., Tice T. R. Biodegradable microspheres: vaccine delivery system for oral immunization. Curr Top Microbiol Immunol. 1989;146:59–66. doi: 10.1007/978-3-642-74529-4_6. [DOI] [PubMed] [Google Scholar]
  7. FORMAL S. B., DAMMIN G. J., LABREC E. H., SCHNEIDER H. Experimental Shigella infections: characteristics of a fatal infection produced in guinea pigs. J Bacteriol. 1958 May;75(5):604–610. doi: 10.1128/jb.75.5.604-610.1958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Forrest B. D., LaBrooy J. T., Robinson P., Dearlove C. E., Shearman D. J. Specific immune response in the human respiratory tract following oral immunization with live typhoid vaccine. Infect Immun. 1991 Mar;59(3):1206–1209. doi: 10.1128/iai.59.3.1206-1209.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Freihorst J., Merrick J. M., Ogra P. L. Effect of oral immunization with Pseudomonas aeruginosa on the development of specific antibacterial immunity in the lungs. Infect Immun. 1989 Jan;57(1):235–238. doi: 10.1128/iai.57.1.235-238.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hale T. L., Bonventre P. F. Shigella infection of Henle intestinal epithelial cells: role of the bacterium. Infect Immun. 1979 Jun;24(3):879–886. doi: 10.1128/iai.24.3.879-886.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kimura A., Mountzouros K. T., Relman D. A., Falkow S., Cowell J. L. Bordetella pertussis filamentous hemagglutinin: evaluation as a protective antigen and colonization factor in a mouse respiratory infection model. Infect Immun. 1990 Jan;58(1):7–16. doi: 10.1128/iai.58.1.7-16.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kopecko D. J., Washington O., Formal S. B. Genetic and physical evidence for plasmid control of Shigella sonnei form I cell surface antigen. Infect Immun. 1980 Jul;29(1):207–214. doi: 10.1128/iai.29.1.207-214.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Labrec E. H., Schneider H., Magnani T. J., Formal S. B. EPITHELIAL CELL PENETRATION AS AN ESSENTIAL STEP IN THE PATHOGENESIS OF BACILLARY DYSENTERY. J Bacteriol. 1964 Nov;88(5):1503–1518. doi: 10.1128/jb.88.5.1503-1518.1964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lee L. A., Shapiro C. N., Hargrett-Bean N., Tauxe R. V. Hyperendemic shigellosis in the United States: a review of surveillance data for 1967-1988. J Infect Dis. 1991 Nov;164(5):894–900. doi: 10.1093/infdis/164.5.894. [DOI] [PubMed] [Google Scholar]
  15. Levenson V. I., Egorova T. P., Belkin Z. P., Fedosova V. G., Subbotina J. L., Rukhadze E. Z., Dzhikidze E. K., Stassilevich Z. K. Protective ribosomal preparation from Shigella sonnei as a parenteral candidate vaccine. Infect Immun. 1991 Oct;59(10):3610–3618. doi: 10.1128/iai.59.10.3610-3618.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lowell G. H., Ballou W. R., Smith L. F., Wirtz R. A., Zollinger W. D., Hockmeyer W. T. Proteosome-lipopeptide vaccines: enhancement of immunogenicity for malaria CS peptides. Science. 1988 May 6;240(4853):800–802. doi: 10.1126/science.2452484. [DOI] [PubMed] [Google Scholar]
  17. Lowell G. H., Smith L. F., Artenstein M. S., Nash G. S., MacDermott R. P., Jr Antibody-dependent cell-mediated antibacterial activity of human mononuclear cells. I. K lymphocytes and monocytes are effective against meningococi in cooperation with human imune sera. J Exp Med. 1979 Jul 1;150(1):127–137. doi: 10.1084/jem.150.1.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lowell G. H., Smith L. F., Griffiss J. M., Brandt B. L. IgA-dependent, monocyte-mediated, antibacterial activity. J Exp Med. 1980 Aug 1;152(2):452–457. doi: 10.1084/jem.152.2.452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lowell G. H., Smith L. F., Seid R. C., Zollinger W. D. Peptides bound to proteosomes via hydrophobic feet become highly immunogenic without adjuvants. J Exp Med. 1988 Feb 1;167(2):658–663. doi: 10.1084/jem.167.2.658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mallett C. P., VanDeVerg L., Collins H. H., Hale T. L. Evaluation of Shigella vaccine safety and efficacy in an intranasally challenged mouse model. Vaccine. 1993;11(2):190–196. doi: 10.1016/0264-410x(93)90016-q. [DOI] [PubMed] [Google Scholar]
  21. Nedrud J. G., Liang X. P., Hague N., Lamm M. E. Combined oral/nasal immunization protects mice from Sendai virus infection. J Immunol. 1987 Nov 15;139(10):3484–3492. [PubMed] [Google Scholar]
  22. Orr N., Arnon R., Rubin G., Cohen D., Bercovier H., Lowell G. H. Enhancement of anti-Shigella lipopolysaccharide (LPS) response by addition of the cholera toxin B subunit to oral and intranasal proteosome-Shigella flexneri 2a LPS vaccines. Infect Immun. 1994 Nov;62(11):5198–5200. doi: 10.1128/iai.62.11.5198-5200.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Orr N., Robin G., Cohen D., Arnon R., Lowell G. H. Immunogenicity and efficacy of oral or intranasal Shigella flexneri 2a and Shigella sonnei proteosome-lipopolysaccharide vaccines in animal models. Infect Immun. 1993 Jun;61(6):2390–2395. doi: 10.1128/iai.61.6.2390-2395.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Reed W. P. Serum factors capable of opsonizing Shigella for phagocytosis by polymorphonuclear neutrophils. Immunology. 1975 Jun;28(6):1051–1059. [PMC free article] [PubMed] [Google Scholar]
  25. Shahin R. D., Amsbaugh D. F., Leef M. F. Mucosal immunization with filamentous hemagglutinin protects against Bordetella pertussis respiratory infection. Infect Immun. 1992 Apr;60(4):1482–1488. doi: 10.1128/iai.60.4.1482-1488.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Stein K. E. Thymus-independent and thymus-dependent responses to polysaccharide antigens. J Infect Dis. 1992 Jun;165 (Suppl 1):S49–S52. doi: 10.1093/infdis/165-supplement_1-s49. [DOI] [PubMed] [Google Scholar]
  27. Stoll B. J., Glass R. I., Huq M. I., Khan M. U., Banu H., Holt J. Epidemiologic and clinical features of patients infected with Shigella who attended a diarrheal disease hospital in Bangladesh. J Infect Dis. 1982 Aug;146(2):177–183. doi: 10.1093/infdis/146.2.177. [DOI] [PubMed] [Google Scholar]
  28. Tacket C. O., Binion S. B., Bostwick E., Losonsky G., Roy M. J., Edelman R. Efficacy of bovine milk immunoglobulin concentrate in preventing illness after Shigella flexneri challenge. Am J Trop Med Hyg. 1992 Sep;47(3):276–283. doi: 10.4269/ajtmh.1992.47.276. [DOI] [PubMed] [Google Scholar]
  29. Tagliabue A., Boraschi D., Villa L., Keren D. F., Lowell G. H., Rappuoli R., Nencioni L. IgA-dependent cell-mediated activity against enteropathogenic bacteria: distribution, specificity, and characterization of the effector cells. J Immunol. 1984 Aug;133(2):988–992. [PubMed] [Google Scholar]
  30. Tagliabue A., Nencioni L., Villa L., Keren D. F., Lowell G. H., Boraschi D. Antibody-dependent cell-mediated antibacterial activity of intestinal lymphocytes with secretory IgA. Nature. 1983 Nov 10;306(5939):184–186. doi: 10.1038/306184a0. [DOI] [PubMed] [Google Scholar]
  31. Taylor D. N., Trofa A. C., Sadoff J., Chu C., Bryla D., Shiloach J., Cohen D., Ashkenazi S., Lerman Y., Egan W. Synthesis, characterization, and clinical evaluation of conjugate vaccines composed of the O-specific polysaccharides of Shigella dysenteriae type 1, Shigella flexneri type 2a, and Shigella sonnei (Plesiomonas shigelloides) bound to bacterial toxoids. Infect Immun. 1993 Sep;61(9):3678–3687. doi: 10.1128/iai.61.9.3678-3687.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. VOINO-YASENETSKY M. V., VOINO-YASENETSKAYA M. K. Experimental pneumonia caused by bacteria of the Shigella group. Acta Morphol Acad Sci Hung. 1962;11:439–454. [PubMed] [Google Scholar]
  33. Wetzler L. M. Immunopotentiating ability of neisserial major outer membrane proteins. Use as an adjuvant for poorly immunogenic substances and potential use in vaccines. Ann N Y Acad Sci. 1994 Aug 15;730:367–370. doi: 10.1111/j.1749-6632.1994.tb44295.x. [DOI] [PubMed] [Google Scholar]
  34. van de Verg L. L., Mallett C. P., Collins H. H., Larsen T., Hammack C., Hale T. L. Antibody and cytokine responses in a mouse pulmonary model of Shigella flexneri serotype 2a infection. Infect Immun. 1995 May;63(5):1947–1954. doi: 10.1128/iai.63.5.1947-1954.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]

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