Mucosal Immunity

  • Michael W. Russell
Part of the Medical Intelligence Unit book series (MIUN)


A perceptive reader scanning the Contents of this volume will notice that of 16 bacterial infections covered, only one (Borrelia burgdorferi) is normally delivered transcutaneously by arthropod bite; the remaining 15 either directly afflict, or normally invade across a mucosal surface. There is nothing unusual about this, as it applies to the great majority of human bacterial and viral infections, with malaria (a protozoal infection) being numerically the most important exception. The immune system counters this threat by deploying the majority of its resources at the mucosae (Fig. 1), so that IgA is produced in quantities that exceed all other immunoglobulin isotypes combined (Table 1), most of this being secretory IgA (S-IgA). There also are more lymphocytes present in the intestinal tract than in all lymphoid organs combined.1,2 Viewed from this standpoint, mucosal protection is the predominant preoccupation of the entire immune system. Therefore, one may ask why there has not been a greater emphasis on developing vaccines that would elicit protection at the portal of entry of pathogens; the oral polio vaccine remains the only human mucosally delivered vaccine that has been widely adopted, although several others are at various stages of development. Part of the reason must be the undoubted success of many vaccines that have been developed for parenteral administration, although most of those in routine use are against invasive viral or toxigenic bacterial diseases, and they work largely by inducing serum neutralizing antibodies.


Cholera Toxin Mucosal Immunity Mucosal Immune System Mucosal Immune Response Mucosal Vaccine 
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  1. 1.
    Brandtzaeg P. Overview of the mucosal immune system. Curr Topics Microbiol Immunol 1989; 146:13–25.CrossRefGoogle Scholar
  2. 2.
    Mestecky J, McGhee JR. Immunoglobulin A (IgA): Molecular and cellular interactions involved in IgA biosynthesis and immune response. Adv Immunol 1987; 40:153–245.Google Scholar
  3. 3.
    Mestecky J, Bienenstock J, McGhee JR et al. Historical aspects of mucosal immunology. In: Ogra PL, Mestecky J, Lamm ME, eds. Mucosal Immunology. 2nd Edition. San Diego: Academic Press, 1999:xxiii–xliii.Google Scholar
  4. 4.
    Mowat AM, Weiner HL. Oral tolerance. Physiological basis and clinical applications. In: Ogra PL, Mestecky J, Lamm ME, eds. Mucosal Immunology. 2nd ed. San Diego: Academic Press, 1999:587–618.Google Scholar
  5. 5.
    Harrod T, Martin M, Russell MW. Long-term persistence and recall of immune responses in aged mice after mucosal immunization. Oral Microbiol Immunol 2001; 16:170–177.PubMedCrossRefGoogle Scholar
  6. 6.
    Harokopakis E, Hajishengallis G, Greenway TE et al. Mucosal immunogenicity of a recombinant Salmonella typhimurium-cloned heterologous antigen in the absence or presence of coexpressed cholera toxin A2/B subunits. Infect Immun 1997; 65:1445–1454.PubMedGoogle Scholar
  7. 7.
    Kohler JJ, Pathangey L, Hasona A et al. Long-term immunological memory induced by recombinant oral Salmonella vaccine vectors. Infect Immun 2000; 68:4370–4373.PubMedCrossRefGoogle Scholar
  8. 8.
    Matzinger P. Tolerance, danger, and the extended family. Annu Rev Immunol 1994; 12:991–1045.PubMedCrossRefGoogle Scholar
  9. 9.
    Ogra PL, Faden H, Welliver RC. Vaccination strategies for mucosal immune responses. Clin Microbiol Rev 2001; 14:430–445.PubMedCrossRefGoogle Scholar
  10. 10.
    Mestecky J, McGhee JR, Michalek SM et al. Concept of the local and common mucosal immune response. Adv Exp Med Biol 1978; 107:185–192.PubMedCrossRefGoogle Scholar
  11. 11.
    Wu HY, Abdu S, Stinson D et al. Generation of female genital tract antibody responses by local or central (common) mucosal immunization. Infect Immun 2000; 68:5539–5545.PubMedCrossRefGoogle Scholar
  12. 12.
    Mestecky J. The common mucosal immune system and current strategies for induction of immune response in external secretions. J Clin Immunol 1987; 7:265–276.PubMedCrossRefGoogle Scholar
  13. 13.
    Kraehenbuhl J-P, Neutra MR. Molecular and cellular basis of immune protection of mucosal surfaces. Physiol Rev 1992; 72:853–879.PubMedGoogle Scholar
  14. 14.
    Fagarasan S, Kinoshita K, Muramatsu M et al. In situ class switching and differentiation to IgA-producing cells in the gut lamina propria. Nature 2001; 413:639–643.PubMedCrossRefGoogle Scholar
  15. 15.
    Butcher EC. Lymphocyte homing and intestinal immunity. In: Ogra PL, Mestecky J, Lamm ME, eds. Mucosal Immunology. 2nd ed. San Diego: Academic Press, 1999:507–522.Google Scholar
  16. 16.
    Quiding-Järbrink M, Nordström I, Granström G et al. Differential expression of tissue-specific adhesion molecules on human circulating antibody-forming cells after systemic, enteric, and nasal immunizations. A molecular basis for the compartmentalization of effector B cell responses. J Clin Invest 1997; 99:1281–1286.PubMedCrossRefGoogle Scholar
  17. 17.
    Johansson EL, Rudin A, Wassén L et al. Distribution of lymphocytes and adhesion molecules in human cervix and vagina. Immunology 1999; 96:272–277.PubMedCrossRefGoogle Scholar
  18. 18.
    Mostov K, Kaetzel CS. Immunoglobulin transport and the polymeric immunoglobulin receptor. In: Ogra PL, Mestecky J, Lamm ME, eds. Mucosal Immunology. 2nd ed. San Diego: Academic Press, 1999:181–211.Google Scholar
  19. 19.
    Mestecky J, Lue C, Russell MW. Selective transport of IgA: cellular and molecular aspects. Gastroenterol Clin N Amer 1991; 20:441–471.Google Scholar
  20. 20.
    McGhee JR, Lamm ME, Strober W. Mucosal immune responses. An overview. In: Ogra PL, Mestecky J, Lamm ME, eds. Mucosal Immunology. 2nd ed. San Diego: Academic Press, 1999: 485–506.Google Scholar
  21. 21.
    Lefrancois L, Puddington L. Basic aspects of intraepithelial lymphocyte immunobiology. In: Ogra PL, Mestecky J, Lamm ME, eds. Mucosal Immunology. 2nd ed. San Diego: Academic Press, 1999:413–428.Google Scholar
  22. 22.
    Aranda R, Sydora BC, Kronenberg M. Intraepithelial lymphocytes: function. In: Ogra PL, Mestecky J, Lamm ME, eds. Mucosal Immunology. 2nd ed. San Diego: Academic Press, 1999:429–437.Google Scholar
  23. 23.
    Fujihashi K, Ernst PB. A mucosal internet. Epithelial cell-immune cell interactions. In: Ogra PL, Mestecky J, Lamm ME, eds. Mucosal Immunology. 2nd ed. San Diego: Academic Press, 1999:619–630.Google Scholar
  24. 24.
    Norderhaug IN, Johansen FE, Schjerven H et al. Regulation of the formation and external transport of secretory immunoglobulins. Crit Rev Immunol 1999; 19:481–508.PubMedGoogle Scholar
  25. 25.
    Mayer L, Blumberg RS. Antigen-presenting cells. Epithelial cells. In: Ogra PL, Mestecky J, Lamm ME, eds. Mucosal Immunology. 2nd ed. San Diego: Academic Press, 1999:365–379.Google Scholar
  26. 26.
    O’Hagan DT, MacKichan ML, Singh M. Recent developments in adjuvants for vaccines against infectious diseases. Biomol Eng 2001; 18:69–85.PubMedCrossRefGoogle Scholar
  27. 27.
    Pizza M, Giuliani MM, Fontana MR et al. Mucosal vaccines: non toxic derivatives of LT and CT as mucosal adjuvants. Vaccine 2001; 19:2534–2541.PubMedCrossRefGoogle Scholar
  28. 28.
    Michalek SM, O’Hagan DT, Gould-Fougerite S et al. Antigen delivery systems. Nonliving microparticles, liposomes, cochleates, and ISCOMS. In: Ogra PL, Mestecky J, Lamm ME, eds. Mucosal Immunology. 2nd ed. San Diego: Academic Press, 1999:759–778.Google Scholar
  29. 29.
    Hantman MJ, Hohmann EL, Murphy CG et al. Antigen delivery systems. Development of recombinant live vaccines using viral or bacterial vectors. In: Ogra PL, Mestecky J, Lamm ME, eds. Mucosal Immunology. 2nd ed. San Diego: Academic Press, 1999:779–791.Google Scholar
  30. 30.
    Wu H-Y, Russell MW. Induction of mucosal immunity by intranasal application of a streptococcal surface protein antigen with the cholera toxin B subunit. Infect Immun 1993; 61:314–322.PubMedGoogle Scholar
  31. 31.
    Gallichan WS, Johnson DC, Graham FL et al. Mucosal immunity and protection after intranasal immunization with recombinant adenovirus expressing herpes simplex virus glycoprotein B. J Infect Dis 1993; 168:622–629.PubMedCrossRefGoogle Scholar
  32. 32.
    Russell MW, Moldoveanu Z, White PL et al. Salivary, nasal, genital, and systemic antibody responses in monkeys immunized intranasally with a bacterial protein antigen and the cholera toxin B sub-unit. Infect Immun 1996; 64:1272–1283.PubMedGoogle Scholar
  33. 33.
    Staats HF, Montgomery SP, Palker TJ. Intranasal immunization is superior to vaginal, gastric, or rectal immunization for the induction of systemic and mucosal anti-HIV antibody responses. AIDS Res Hum Retroviruses 1997; 13:945–952.PubMedCrossRefGoogle Scholar
  34. 34.
    Hashigucci K, Ogawa H, Ishidate T et al. Antibody responses in volunteers induced by nasal influenza vaccine combined with Escherichia coli heat-labile enterotoxin B subunit containing a trace amount of the holotoxin. Vaccine 1996; 14:113–119.PubMedCrossRefGoogle Scholar
  35. 35.
    Haneberg B, Dalseg R, Wedege E et al. Intranasal administration of a meningococcal outer membrane vesicle vaccine induces persistent local mucosal antibodies and serum antibodies with strong bactericidal activity in humans. Infect Immun 1998; 66:1334–1341.PubMedGoogle Scholar
  36. 36.
    Rudin A, Johansson E-L, Bergquist C et al. Differential kinetics and distribution of antibodies in serum and nasal and vaginal secretions after nasal and oral vaccination of humans. Infect Immun 1998; 66:3390–3396.PubMedGoogle Scholar
  37. 37.
    Belshe RB, Mendelman PM, Treanor J et al. The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children. N Engl J Med 1998; 338:1405–1412.PubMedCrossRefGoogle Scholar
  38. 38.
    Vajdy M, Lycke N. Stimulation of antigen-specific T- and B-cell memory in local as well as systemic lymphoid tissues following oral immunization with cholera toxin adjuvant. Immunology 1993; 80:197–203.PubMedGoogle Scholar
  39. 39.
    Jertborn M, Svennerholm AM, Holmgren J. Immunological memory after immunization with oral cholera B subunit-whole-cell vaccine in Swedish volunteers. Vaccine 1994; 12:1078–1082.PubMedCrossRefGoogle Scholar
  40. 40.
    Sack DA, Clemens JD, Huda S et al. Antibody responses after immunization with killed oral cholera vaccines during the 1985 vaccine field trial in Bangladesh. J Infect Dis 1991; 164:407–411.PubMedCrossRefGoogle Scholar
  41. 41.
    Klipstein FA, Engert RF, Clements JD. Arousal of mucosal secretory immunoglobulin A antitoxin in rats immunized with Escherichia coli heat-labile enterotoxin. Infect Immun 1982; 37:1086–1092.PubMedGoogle Scholar
  42. 42.
    Clements JD, Hartzog NM, Lyon FL. Adjuvant activity of Escherichia coli heat-labile enterotoxin and effect on the induction of oral tolerance in mice to unrelated protein antigens. Vaccine 1988; 6:269–277.PubMedCrossRefGoogle Scholar
  43. 43.
    Elson CO. Cholera toxin and its subunits as potential oral adjuvants. Curr Topics Microbiol Immunol 1989; 146:29–33.CrossRefGoogle Scholar
  44. 44.
    Lycke N, Tsuji T, Holmgren J. The adjuvant effect of Vibrio cholerae and Escherichia coli heat-labile enterotoxins is linked to their ADP-ribosyltransferase activity. Eur J Immunol 1992; 22:2277–2281.PubMedCrossRefGoogle Scholar
  45. 45.
    Tamura S, Yamanaka A, Shimohara M et al. Synergistic action of cholera toxin B subunit (and Escherichia coli heat-labile toxin B subunit) and a trace amount of cholera whole toxin as an adjuvant for nasal influenza vaccine. Vaccine 1994; 12:419–426.PubMedCrossRefGoogle Scholar
  46. 46.
    de Haan L, Verweij WR, Feil IK et al. Mutants of the Escherichia coli heat-labile enterotoxin with reduced ADP-ribosylation activity or no activity retain the immunogenic properties of the native holotoxin. Infect Immun 1996; 64:5413–5416.PubMedGoogle Scholar
  47. 47.
    Wu HY, Russell MW. Induction of mucosal and systemic immune responses by intranasal immunization using recombinant cholera toxin B subunit as an adjuvant. Vaccine 1998; 16:286–292.PubMedCrossRefGoogle Scholar
  48. 48.
    Wilson AD, Clarke CJ, Stokes CR. Whole cholera toxin and B subunit act synergistically as an adjuvant for the mucosal immune response of mice to keyhole limpet haemocyanin. Scand J Immunol 1990; 31:443–451.PubMedCrossRefGoogle Scholar
  49. 49.
    Elson CO, Dertzbaugh MT. Mucosal adjuvants. In: Ogra PL, Mestecky J, Lamm ME, eds. Mucosal Immunology. 2nd ed. San Diego: Academic Press, 1999:817–838.Google Scholar
  50. 50.
    Martin MH, Metzger DJ, Michalek SM et al. Comparative analysis of the mucosal adjuvanticity of the type II heat-labile enterotoxins, LT-IIa and LT-IIb. Infect Immun 2000; 68:281–287.PubMedCrossRefGoogle Scholar
  51. 51.
    Martin MH, Metzger DJ, Michalek SM et al. Distinct cytokine regulation by cholera toxin and the type II heat-labile enterotoxins involves differential regulation of CD40 ligand on CD4+ T cells. Infect Immun 2001; 69:4486–4492.PubMedCrossRefGoogle Scholar
  52. 52.
    Porgador A, Staats HF, Itoh Y et al. Intranasal immunization with cytotoxic T-lymphocyte epitope peptide and mucosal adjuvant cholera toxin: Selective augmentation of peptide-presenting dendritic cells in nasal mucosa-associated lymphoid tissue. Infect Immun 1998; 66:5876–5881.PubMedGoogle Scholar
  53. 53.
    Belyakov IM, Ahlers JD, Clements JD et al. Interplay of cytokines and adjuvants in the regulation of mucosal and systemic HIV-specific CTL. J Immunol 2000; 165:6454–6462.PubMedGoogle Scholar
  54. 54.
    Van Ginkel FW, Jackson RJ, Yuki Y et al. Cutting edge: The mucosal adjuvant cholera toxin redirects vaccine proteins into olfactory tissues. J Immunol 2000; 165:4778–4782.PubMedGoogle Scholar
  55. 55.
    Hagiwara Y, Iwasaki T, Asanuma H et al. Effects of intranasal administration of cholera toxin (or Escherichia coli heat-labile enterotoxin) B subunits supplemented with a trace amount of the holotoxin on the brain. Vaccine 2001; 19:1652–1660.PubMedCrossRefGoogle Scholar
  56. 56.
    Russell MW, Wu H-Y. Distribution, persistence, and recall of serum and salivary antibody responses to peroral immunization with protein antigen I/II of Streptococcus mutans coupled to the cholera toxin B subunit. Infect Immun 1991; 59:4061–4070.PubMedGoogle Scholar
  57. 57.
    Dertzbaugh MT, Peterson DL, Macrina FL. Cholera toxin B-subunit gene fusion: structural and functional analysis of the chimeric protein. Infect Immun 1990; 58:70–79.PubMedGoogle Scholar
  58. 58.
    Jagusztyn-Krynicka EK, Clark-Curtiss JE, Curtiss R. Escherichia coli heat-labile toxin subunit B fusions with Streptococcus sobrinus antigens expressed by Salmonella typhimurium oral vaccine strains: importance of the linker for antigenicity and biological activities of the hybrid proteins. Infect Immun 1993; 61:1004–1015.PubMedGoogle Scholar
  59. 59.
    Hajishengallis G, Hollingshead SK, Koga T et al. Mucosal immunization with a bacterial protein antigen genetically coupled to cholera toxin A2/B subunits. J Immunol 1995; 154:4322–4332.PubMedGoogle Scholar
  60. 60.
    Jobling MG, Holmes RK. Fusion proteins containing the A2 domain of cholera toxin assemble with B polypeptides of cholera toxin to form immunoreactive and functional holotoxin-like chimeras. Infect Immun 1992; 60:4915–4924.PubMedGoogle Scholar
  61. 61.
    Sultan F, Jin LL, Jobling MG et al. Mucosal immunogenicity of a holotoxin-like molecule containing the serine-rich Entamoeba histolytica protein (SREHP) fused to the A2 domain of cholera toxin. Infect Immun 1998; 66:462–468.PubMedGoogle Scholar
  62. 62.
    Hajishengallis G, Russell MW, Michalek SM. Effectiveness of an adherence domain in comparison to a structural domain of Streptococcus mutans antigen I/II in protection against dental caries in rats after intranasal immunization. Infect Immun 1998; 66:1740–1743.PubMedGoogle Scholar
  63. 63.
    Sun JB, Holmgren J, Czerkinsky C. Cholera toxin B subunit: An efficient transmucosal carrier-delivery system for induction of peripheral immunological tolerance. Proc Natl Acad Sci USA 1994; 91:10795–10799.PubMedCrossRefGoogle Scholar
  64. 64.
    Grdic D, Smith R, Donachie A et al. The mucosal adjuvant effects of cholera toxin and immune-stimulating complexes differ in their requirement for IL-12, indicating different pathways of action. Eur J Immunol 1999; 29:1774–1784.PubMedCrossRefGoogle Scholar
  65. 65.
    Gizurarson S. Optimal delivery of vaccines: clinical pharmacokinetic considerations. Clin Pharmacokinet 1996; 30:1–15.PubMedCrossRefGoogle Scholar
  66. 66.
    Harokopakis E, Hajishengallis G, Michalek SM. Effectiveness of liposomes possessing surface-linked recombinant B subunit of cholera toxin as an oral antigen delivery system. Infect Immun 1998; 66:4299–4304.PubMedGoogle Scholar
  67. 67.
    Curtiss R, Kelly SM, Gulig PA et al. Selective delivery of antigens by recombinant bacteria. Curr Topics Microbiol Immunol 1989; 146:35–49.CrossRefGoogle Scholar
  68. 68.
    Carter PB, Collins FM. The route of enteric infection in normal mice. J Exp Med 1974; 139:1189–1203.PubMedCrossRefGoogle Scholar
  69. 69.
    Galan JE, Nakayama K, Curtiss R. Cloning and characterization of the asd gene of Salmonella typhimurium: use in stable maintenance of recombinant plasmids in Salmonella vaccine strains. Gene 1990; 94:29–35.PubMedCrossRefGoogle Scholar
  70. 70.
    Roberts M, Bacon A, Li JL et al. Prior immunity to homologous and heterologous Salmonella serotypes suppresses local and systemic anti-fragment C antibody responses and protection from tetanus toxin in mice immunized with Salmonella strains expressing fragment C. Infect Immun 1999; 67:3810–3815.PubMedGoogle Scholar
  71. 71.
    Kohler JJ, Pathangey LB, Gillespie SR et al. Effect of preexisting immunity to Salmonella on the immune response to recombinant Salmonella enterica serovar Typhimurium expressing a Porphyromonas gingivalis hemagglutinin. Infect Immun 2000; 68:3116–3120.PubMedCrossRefGoogle Scholar
  72. 72.
    Kumpel GR, Asuncion M, Haithcoat J et al. Cholera toxin and Salmonella typhimurium induce different cytokine profiles in the gastrointestinal tract. Infect Immun 1995; 63:1134–1137.Google Scholar
  73. 73.
    Hajishengallis G, Harokopakis E, Hollingshead SK et al. Construction and oral immunogenicity of a Salmonella typhimurium strain expressing a streptococcal adhesin linked to the A2/B subunits of cholera toxin. Vaccine 1996; 14:1545–1548.PubMedCrossRefGoogle Scholar
  74. 74.
    Huang Y, Hajishengallis G, Michalek SM. Construction and characterization of a Salmonella enterica serovar Typhimurium clone expressing a salivary adhesin of Streptococcus mutans under control of the anaerobically inducible nirB promoter. Infect Immun 2000; 68:1549–1556.PubMedCrossRefGoogle Scholar
  75. 75.
    Medaglini D, Pozzi G, King TP et al. Mucosal and systemic immune responses to a recombinant protein expressed on the surface of the oral commensal bacterium Streptococcus gordonii after oral colonization. Proc Natl Acad Sci USA 1995; 92:6868–6872.PubMedCrossRefGoogle Scholar
  76. 76.
    Shaw DM, Gaerthé B, Leer RJ et al. Engineering the microflora to vaccinate the mucosa: serum immunoglobulin G responses and activated draining cervical lymph nodes following mucosal application of tetanus toxin fragment C-expressing lactobacilli. Immunology 2000; 100:510–518.PubMedCrossRefGoogle Scholar
  77. 77.
    Shroff KE, Meslin K, Cebra JJ. Commensal enteric bacteria engender a self-limiting humoral mucosal immune response while permanently colonizing the gut. Infect Immun 1995; 63:3904–3913.PubMedGoogle Scholar
  78. 78.
    Palmer KE, Arntzen CJ, Lomonossoff GP. Antigen delivery systems.Transgenic plants and recombinant plant viruses. In: Ogra PL, Mestecky J, Lamm ME, eds. Mucosal Immunology. 2nd ed. San Diego: Academic Press, 1999:793–807.Google Scholar
  79. 79.
    Thanavala Y, Yang YF, Lyons P et al. Immunogenicity of transgenic plant-derived hepatitis B surface antigen. Proc Natl Acad Sci USA 1995; 92:3358–3361.PubMedCrossRefGoogle Scholar
  80. 80.
    Mason HS, Haq TA, Clements JD et al. Edible vaccine protects mice against Escherichia coli heat-labile enterotoxin (LT): potatoes expressing a synthetic LT-B gene. Vaccine 1998; 16:1336–1343.PubMedCrossRefGoogle Scholar
  81. 81.
    Fynan EF, Webster RG, Fuller DH et al. DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations. Proc Natl Acad Sci USA 1993; 90:11478–11482.PubMedCrossRefGoogle Scholar
  82. 82.
    Livingston JB, Lu S, Robinson H et al. Immunization of the female genital tract with a DNA-based vaccine. Infect Immun 1998; 66:322–329.PubMedGoogle Scholar
  83. 83.
    Van Ginkel FWy Liu C, Simecka JW et al. Intratracheal gene delivery with adenoviral vector induces elevated systemic IgG and mucosal IgA antibodies to adenovirus and beta-galactosidase. Hum Gene Ther 1995; 6:895–903.CrossRefGoogle Scholar
  84. 84.
    Sizemore DR, Branstrom AA, Sadoff JC. Attenuated Shigella as a DNA delivery vehicle for DNA-mediated immunization. Science 1995; 270:299–302.PubMedCrossRefGoogle Scholar
  85. 85.
    Wu Y, Wang X, Csencsits KL et al. M cell-targeted DNA vaccination. Proc Natl Acad Sci USA 2001; 98:9318–9323.PubMedCrossRefGoogle Scholar
  86. 86.
    McCluskie MJ, Weeratna RD, Krieg AM et al. CpG DNA is an effective oral adjuvant to protein antigens in mice. Vaccine 2000; 19:950–957.PubMedCrossRefGoogle Scholar
  87. 87.
    Briles DE, Ades E, Paton JC et al. Intranasal immunization of mice with a mixture of the pneumococcal proteins PsaA and PspA is highly protective against nasopharyngeal carriage of Streptococcus pneumoniae. Infect Immun 2000; 68:796–800.PubMedCrossRefGoogle Scholar
  88. 88.
    Russell MW, Martin MH, Wu H-Y et al. Strategies of immunization against mucosal infections. Vaccine 2001; 19 (Suppl. l):S122–S127.Google Scholar
  89. 89.
    Suzuki M, Kawauchi H, Mogi G. Immune-mediated otitis media with effusion. Am J Otolaryngol 1988; 9:199–209.PubMedCrossRefGoogle Scholar
  90. 90.
    Sparling PF, Elkins C, Wyrick PB et al. Vaccines for bacterial sexually transmitted infections: A realistic goal? Proc Natl Acad Sci USA 1994; 91:2456–2463.PubMedCrossRefGoogle Scholar
  91. 91.
    Mestecky J, Russell MW. Induction of mucosal immune responses in the genital tract. FEMS Immunol Med Microbiol 2000; 27:351–355.PubMedCrossRefGoogle Scholar
  92. 92.
    Gallichan WS, Rosenthal KL. Specific secretory immune responses in the female genital tract following intranasal immunization with a recombinant adenovirus expressing glycoprotein B of herpes simplex virus. Vaccine 1995; 13:1589–1595.PubMedCrossRefGoogle Scholar
  93. 93.
    Johansson E-L, Wassen L, Holmgren J et al. Nasal and vaginal vaccinations have differential effects on antibody responses in vaginal and cervical secretions in humans. Infect Immun 2001; 69:7481–7486.PubMedCrossRefGoogle Scholar
  94. 94.
    Rudin G, Riise GC, Holmgren J. Antibody responses in the lower respiratory tract and male urogenital tract in humans after nasal and oral vaccination with cholera toxin B subunit. Infect Immun 1999; 67:2884–2890.PubMedGoogle Scholar
  95. 95.
    Parr EL, Parr MB. Immune responses and protection against vaginal infection after nasal or vaginal immunization with attenuated herpes simplex virus type-2. Immunology 1999; 98:639–645.PubMedCrossRefGoogle Scholar
  96. 96.
    Valnes K, Brandtzaeg P, Elgjo K et al. Quantitative distribution of immunoglobulin-producing cells in gastric mucosa: relation to chronic gastritis and glandular atrophy. Gut 1986; 27:505–514.PubMedCrossRefGoogle Scholar
  97. 97.
    Ahlstedt I, Lindholm C, Lönroth H et al. Role of local cytokines in increased gastric expression of the secretory component in Helicobacter pylori infection. Infect Immun 1999; 67:4921–4925.PubMedGoogle Scholar
  98. 98.
    Czinn SJ, Nedrud JG. Oral immunization against Helicobacter pylori. Infect Immum 1991; 59:2359–2363.Google Scholar
  99. 99.
    Weltzin R, Guy B, Thomas Jr WD et al. Parenteral adjuvant activities of Escherichia coli heat-labile toxin and its B subunit for immunization of mice against gastric Helicobacter pylori infection. Infect Immun 2000; 68:2775–2782.PubMedCrossRefGoogle Scholar
  100. 100.
    Hatzifoti C, Wren BW, Morrow WJW. Helicobacter pylori vaccine strategies — triggering a gut reaction. Immunol Today 2000; 21:615–619.PubMedCrossRefGoogle Scholar
  101. 101.
    Loesche WJ, Grossman NS. Periodontal disease as a specific, albeit chronic, infection: diagnosis and treatment. Clin Microbiol Rev 2001; 14:727–752.PubMedCrossRefGoogle Scholar
  102. 102.
    Moritz AJ, Cappelli D, Lantz MS et al. Immunization with Porphyromonas gingivalis cysteine protease: Effects on experimental gingivitis and ligature-induced periodontitis in Macaca fascicularis. J Periodontol 1998; 69:686–697.PubMedCrossRefGoogle Scholar
  103. 103.
    Houston LS, Lukehart SA, Persson GR et al. Function of anti-Porphyromonas gingivalis immunoglobulin classes in immunized Macaca fascicularis. Oral Microbiol Immunol 1999;14:86–91.PubMedCrossRefGoogle Scholar
  104. 104.
    Grbic JT, Lamster IB, Fine JB et al. Changes in gingival crevicular fluid levels of immunoglobulin A following therapy: Association with attachment loss. J Periodontol 1999; 70:1221–1227.PubMedCrossRefGoogle Scholar
  105. 105.
    Russell MW, Sibley DA. IgA as an anti-inflammatory regulator of immunity. Oral Dis 1999; 5:55–56.Google Scholar

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