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The Role of Humoral Immunity against Vaginal Candida Infection

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Fungal Immunology

4. Conclusions

Candida is essentially an extracellular organism and, as such, Abs against critical antigens for virulence are expected to play a role. This has been dismissed in the light of evidence that cell-mediated immune dysfunctions favor candidiasis. However, this does not exclude any additional or even replacing role of Abs in defined settings. There is now clear experimental evidence that some Abs may indeed be therapeutic; the experiments also suggest that under natural conditions, protective Abs may be obscured by the plethora of irrelevant if not disease-enhancing Abs. The time has now come that not only have Abs been shown to play more than a likely protective role against vaginitis, more importantly, these Abs or their engineered fragments should be used therapeutically. Our findings with protective Abs at the vaginal level may constitute the basis for such a clinical development.

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References

  • Aronson, I.K. and Soltani, K. (1976). Chronic mucocutaneous candidosis: A review. Mycopathologia 60: 17–25.

    Article  CAS  PubMed  Google Scholar 

  • Beninati, C., Oggioni, M.R., Boccanera, M., Spinosa, M.R., Maggi, T., Conti, S., Magliani W., De Bernardis, F., Teti, G., Cassone, A., Pozzi, G., and Polonelli, L. (2000). Therapy of experimental mucosal candidiasis by engineered human commensal bacteria expressing a microbicidal recombinant anti-idiotype. Nat. Biotechnol. 8: 1060–1064.

    Google Scholar 

  • Bevan, E.A., Herring, A.J., and Mitchell, D.J. (1973). Preliminary characterization of two species of dsRNA in yeast and their relation-ship to the “Killer” character. Nature 142: 81–86.

    Google Scholar 

  • Bromuro, C., La Valle, R., Sandini, S., Urbani, F., Ausiello, C.M., Morelli, L., Fe d’Ostiani, C., Romani, L., and Cassone, A. (1998). A 70-kilodalton recombinant heat shock protein of Candida albicans is highly immunogenic and enhances systemic murine candidiasis. Infect. Immun. 66: 2154–2162.

    CAS  PubMed  Google Scholar 

  • Caesar-TonThat, T.C. and Cutler, J.E. (1997). A monoclonal antibody to Candida albicans enhances mouse neutrophil candidacidal activity. Infect. Immun. 65: 5354–5357.

    CAS  PubMed  Google Scholar 

  • Calderone, R. and Fonzi, W. (2001). Virulence factors of Candida albicans. Trends Microbiol. 9: 327–335.

    Article  CAS  PubMed  Google Scholar 

  • Casadevall, A. (1995). Antibody immunity and invasive fungal infections. Infect. Immun. 63: 4211–4218.

    CAS  PubMed  Google Scholar 

  • Casadevall, A., Cassone, A., Bistoni, F., Cutler, J.E., Magliani, W., Murphy, J.W., Polonelli, L., Romani, L. (1998). Antibody and/or cellmediated immunity, protective mechanisms in fungal disease: An ongoing dilemma or an unnecessary dispute? Med. Mycol. 36(S1): 95–105.

    CAS  PubMed  Google Scholar 

  • Casanova, M., Martinez, J.P., Chaffin, W.L. (1990). Fab fragments from a monoclonal antibody against a germ tube mannoprotein block the yeast-to mycelium transition in Candida albicans. Infect. Immun. 58: 3810–3812.

    CAS  PubMed  Google Scholar 

  • Cassone, A. and Torosantucci, A. (1991). Immunological moieties of the cell wall. In R. Prasad (ed.), Candida albicans. Springler-Verlag, Berlin, pp. 89–107.

    Google Scholar 

  • Cassone, A., Boccanera, M., Adriani, D., Santoni, G., and De Bernardis, F. (1995). Rats clearing a vaginal infection by Candida albicans acquire specific, antibody-mediated resistance to vaginal reinfection. Infect. Immun. 63: 2619–2624.

    CAS  PubMed  Google Scholar 

  • Cassone, A., Corti, S., De Bernardis, F., and Polonelli, L. (1997). Antibodies killer toxins and antifungal immunoprotection: A lesson from nature? Immunol. Today 18: 163–169.

    Article  Google Scholar 

  • Cassone, A., De Bernardis, F., Ausiello, C.M., Gomez, M.J., Boccanera, M., La Valle, R., and Torosantucci, A. (1998). Immunogenic and protective Candida albicans constituents. Res. Immunol. 149: 289–299.

    CAS  PubMed  Google Scholar 

  • Cutler, J. (1991). Putative virulence factors of Candida albicans. Annu. Rev. Microbiol. 45: 187–218.

    Article  CAS  PubMed  Google Scholar 

  • Cutler, J.E., Granger, B.L., and Han, Y. (2002). Vaccines, antibodies and passive immunity in candidiasis. In R.A. Calderone and R.L. Cihlar (eds), Fungal Pathogenesis. Marcel Dekker, New York, pp. 243–251.

    Google Scholar 

  • Czerkinnsky, C., Anjuere, F., McGhee, J.R., George-Chandy, A., Holmgren, J., Kieny, M.P., Fujiyashi, K., Mestecky, J.F., Pierrefite-Carle, V., Rask, C., and Sun, J.B. (1999). Mucosal immunity and tolerance: Relevance to vaccine development. Immun. Rev. 170: 197–222.

    Google Scholar 

  • De Bernardis, F., Agatensi, L., Ross, I.K., Emerson, G.W., Lorenzini, R., Sullivan, P.A., and Cassone, A. (1990). Evidence for a role for secreted aspartate proteinase of Candida albicans in vulvovaginal candidiasis. J. Infect. Dis. 161: 1276–1283.

    PubMed  Google Scholar 

  • De Bernardis, F., Cassone, A., Sturtevant, J., and Calderone, R. (1995). Expression of Candida albicans SAP1 and SAP2 in experimental vaginitis. Infect. Immun. 6: 1887–1892.

    Google Scholar 

  • De Bernardis, F., Boccanera, M., Adriani, D., Spreghini, E., Santoni, G., and Cassone, A. (1997). Protective role of antimannan and antiaspartyl proteinase antibodies in an experimental model of Candida albicans vaginitis in rats. Infect. Immun. 65: 3399–3405.

    PubMed  Google Scholar 

  • De Bernardis, F., Muhlschlegel, F.A., Cassone, A., and Fonzi, W.A. (1998). The pH of the host niche controls gene expression in and virulence of Candida albicans. Infect. Immun. 66: 3317–3325.

    PubMed  Google Scholar 

  • De Bernardis, F., Santoni, G., Boccanera, M., Spreghini, E., Adriani, D., Morelli, L., and Cassone, A. (2000). Local anticandidal immune responses in a rat model of vaginal infection by and protection, Candida albicans. Infect. Immun. 68: 3297–3304.

    PubMed  Google Scholar 

  • De Bernardis, F., Boccanera, M., Adriani, D., Girolamo, A., and Cassone, A. (2002). Intravaginal and intranasal immunization are equally effective in inducing vaginal antibodies and conferring protection against vaginal candidiasis. Infect. Immun. 70: 2725–2729.

    PubMed  Google Scholar 

  • De Bernardis, F., Boccanera, M., Amantini, C., and Santoni, G. (2004). T and B lymphocytes in mucosal candidiasis. In G. San-Blas and R. Calderone (eds), Pathogenic Fungi: Host Interaction and Emerging Strategies for Control, Caister Academic Press, UK.

    Google Scholar 

  • Elitsur, Y., Jackman, S., Neace, C., Keerthy, S., Liu, S., Dosescu, J., and Mosheir, J.A. (1998). Human vaginal mucosa Immune system: Characterization and function. Gen. Diagn. Pathol. 143: 271–277.

    CAS  PubMed  Google Scholar 

  • Fidel, P.L. Jr. and Sobel, J.D. (1996). Immunopathogenesis of recurrent vulvovaginal candidiasis. Clin. Microbiol. Rev. 9: 335–348.

    PubMed  Google Scholar 

  • Fidel, P.L. Jr. and Sobel, J.D. (1998). Protective immunity in experimental Candida vaginitis. Res. Immunol. 146: 361–373.

    Google Scholar 

  • Fidel, P.L. Jr. and Sobel, J.D. (2002). Host defense against vaginal candidiasis. In: R.A. Calderone (ed.), Candida and Candidosis, ASM Press, Washington, pp. 193–209.

    Google Scholar 

  • Fidel, P.L., Lynch, M.E., and Sobel, J.D. (1993a). Candida-specific Th1-type responsiveness in mice with experimental vaginal candidiasis. Infect. Immun. 61: 4202–4207.

    PubMed  Google Scholar 

  • Fidel, P.L., Jr., Lynch, M.E., and Sobel, J.D. (1993b). Candida-specific cell-mediated immunity is demonstrable in mice with experimental vaginal candidiasis. Infect. Immun. 61: 1990–1995.

    CAS  PubMed  Google Scholar 

  • Fidel, P.L. Jr., Lynch, M.E., and Sobel, J.D. (1994). Effects of preinduced Candida-specific systemic cell-mediated immunity on experimental vaginal candidiasis. Infect. Immun. 62: 1032–1038.

    PubMed  Google Scholar 

  • Fidel, P.L., Cutright, J.L., and Sobel, J.D. (1995a). Effects of systemic cell-mediated immunity on vaginal candidiasis in mice resistant and susceptible to Candida albicans infections. Infect. Immun. 63: 4191–4194.

    PubMed  Google Scholar 

  • Fidel, P.L. Jr., Lynch, M.E., Conaway, D.H., Tait, L., and Sobel, J.D. (1995b). Mice immunized by primary vaginal Candida albicans infection develop acquired vaginal mucosal immunity. Infect. Immun. 63: 547–553.

    CAS  PubMed  Google Scholar 

  • Fidel, P.L., Lynch, M.E., and Sobel, J.D. (1995c). Circulating CD4 and CD8 T-cells have little impact on host defence against experimental vaginal candidiasis. Infect. Immun. 63: 2403–2408.

    CAS  PubMed  Google Scholar 

  • Fidel, P.L., Wolf, N.A., and Kukuruga, M.A. (1996). T lymphocytes in the murine vaginal mucosa are phenotypically distinct from those in the periphery. Infect. Immun. 64: 3793–3799.

    CAS  PubMed  Google Scholar 

  • Fidel, P.L., Ginsburg, K.A., Cutright, J.L., Wolf, N.A., Leaman, D., Dunlops, K., and Sobel, J.D. (1997a). Vaginal-associated immunity in women with recurrent vulvovaginal candidiasis: Evidence for vaginal Th1-type responses following intravaginal challenge with Candida antigen. J. Infect. Dis. 176: 728–739.

    CAS  PubMed  Google Scholar 

  • Fidel, P.L., Luo, W., Chabain, J., Wolf, N.A., and Vanburen, E. (1997b). Use of cellular depletion analysis to examine circulation of immune effector function between the vagina and the periphery. Infect. Immun. 65: 3939–3943.

    CAS  PubMed  Google Scholar 

  • Fidel, P.L. Jr., Luo, W., Steele, C., Chabain, J., Baker, M., and Wormley, F. Jr. (1999). Analysis of vaginal cell populations during experimental vaginal candidiasis. Infect. Immun. 67: 3135–3140.

    CAS  PubMed  Google Scholar 

  • Garcia-Ruiz, J.C., Del Carmen Arilla, M., Regulez, P., Quindos, G., Alvarez, A., and Ponton, J. (1997). Detection of antibodies to Candida albicans germ tubes for diagnosis and therapeutic monitoring of invasive candidiasis inpatients with hematologic malignancies. J. Clin. Microbiol. 35: 3284–3287.

    CAS  PubMed  Google Scholar 

  • Ghannoum, M.A. and Abu-Elteen, K.H. (1990). Pathogenicity determinant of Candida. Mycoses 33: 265–282.

    CAS  PubMed  Google Scholar 

  • Greenfield, R.A. (1992). Host defense system interaction with Candida. J. Med. Vet. Mycol. 30: 89–104.

    CAS  PubMed  Google Scholar 

  • Guyard, C., Dehecq, E., Tissier, J.P., Polonelli, L, Dei-Cas, E., Cailliez, J.C., and Menozzi, F.D. (2002). Involvement of beta-glucan in the wide spectrum antimicrobial activity Williopsis saturnus var mrakii MUCL 41968 killer toxin. Mol. Med. 8: 686–694.

    CAS  PubMed  Google Scholar 

  • Han, Y., Kanbe, T., Cherniak, R., and Cutler, J. (1997). Biochemical characterization of Candida albicans epitopes that can elicit protective and nonprotective antibodies. Infect. Immun 65: 4100–4107.

    CAS  PubMed  Google Scholar 

  • Han, Y., Morrison, R.P., and Cutler, J.E. (1998). A vaccine and monoclonal antibodies that enhance mouse resistance to Candida albicans vaginal infection. Infect. Immun. 66: 5771–5776.

    CAS  PubMed  Google Scholar 

  • Han, Y., Riesselman, M., and Cutler, J.E. (2000). Protection against candidiasis by an immunoglobulin G3 (IgG3) monoclonal antibody specific for the same mannotriose as an IgM protective antibody. Infect. Immun. 68: 1649–1654.

    CAS  PubMed  Google Scholar 

  • Jones-Carson, J., Vazquez-Torres, A., van der Heyde, T., Warner, T., Wagner, R.D., and Balish, E. (1995). γδ T cell-induced nitric oxide production enhances resistance to mucosal candidiasis. Nat. Med. 6: 552–557.

    Google Scholar 

  • Kinsman, O.S. and Collard, A.E. (1986). Hormonal factors in vaginal candidiasis in rats. Infect. Immun. 53: 498–504.

    CAS  PubMed  Google Scholar 

  • Kinsman, O.S., Collard, A.E., and Savage, T.J. (1986). Ketoconazole in experimental vaginal candidosis in rats. Antimicrob. Agents Chemother. 30: 771–773.

    CAS  PubMed  Google Scholar 

  • Kirkpatrick, C.H., Rich, R.R., and Bennett, J.E. (1971). Chronic mucocutaneous candidiasis: Model-building in cellular immunity. Ann. Intern. Med. 74: 955–978.

    CAS  PubMed  Google Scholar 

  • Magliani, W., Conti, S., De Bernardis, F., Gerloni, M., Bertolotti, D, Mozzoni, P., Cassone, A., and Polonelli, L. (1997). Therapeutic activity of single chain fragment variable yeast-killer toxin-like candidacidal recombinant antiidiotypic antibodies. Nat. Biotechnol. 15: 155–158.

    Article  CAS  PubMed  Google Scholar 

  • Magliani, W., Conti, S., De Bernardis, F., Cassone, A., and Polonelli, L. (2002). New immunotherapeutic strategies to control vaginal candidiasis. Trends Mol. Med. 8: 121–126.

    Article  CAS  PubMed  Google Scholar 

  • Marodi, L. (1997). Local and systemic host defence mechanisms against Candida: Immunopathology of candidal infections. Pediatr. Infect. Dis. 16: 795–801.

    Article  CAS  Google Scholar 

  • McGhee, J.R., Mestecky, J., Elson, C.O., and Kiyono, H. (1989). Regulation of IgA synthesis and immune response by T cells and interleukins. J. Clin. Immun. 9: 175–180.

    CAS  PubMed  Google Scholar 

  • Mourad, S. and Friedman, L. M. (1961). Active immunization of mice against Candida albicans. Proc. Soc. Exp. Biol. Med. 106: 570–572.

    CAS  PubMed  Google Scholar 

  • Mourad, S. and Friedman, L. M. (1968). Passive immunization of mice against Candida albicans. Sabouradia 6: 103–105.

    CAS  Google Scholar 

  • Mulero-Marchese, R.D., Blank, K.J., and Siek, T.G. (1998). Genetic basis for protection against experimental vaginal candidiasis by peripheral immunization. J. Infect. Dis. 178: 227–234.

    CAS  PubMed  Google Scholar 

  • Oggioni, M.R., Beninati, C., Boccanera, M., Medaglini, D., Spinosa, M.R., Maggi, T., Conti, S., Magliani, W., De Bernardis, F., Teti, G., Cassone, A., Pozzi, G., and Polonelli, L. (2001). Recombinant Streptococcus gordonii for mucosal delivery of a scFv microbicidal antibody. Intern. Rev. Immunol. 20: 267–279.

    Google Scholar 

  • Polonelli, L. and Morace, G. (1986). Re-evaluation of the yeast killer phenmenon. J. Clin. Microbiol. 24: 866–869.

    CAS  PubMed  Google Scholar 

  • Polonelli, L. and Morace, G. (1987). Production and characterization of yeast killer toxin monoclonal antibodies. J. Clin. Microbiol. 25: 460–462.

    CAS  PubMed  Google Scholar 

  • Polonelli, L., Conti, S., Gerloni, M., Magliani, W., Chezzi, C., and Morace, G. (1991). Interfaces of the yeast killer phenomenon. Crit. Rev. Microbiol. 18(1): 47–87.

    CAS  PubMed  Google Scholar 

  • Polonelli, L., Lorenzini, R., De Bernardis, F., Gerloni, M., Conti, S., Morace, G., Magliani, W., and Chezzi, C. (1993). Idiotypic vaccination immunoprotection mediated by anti-idiotypic antibodies with antibiotic activity. Scand. J. Immunol. 37: 105–110.

    CAS  PubMed  Google Scholar 

  • Polonelli, L., De Bernardis, F., Conti, S., Boccanera, M., Gerloni, M., Morace, G., Magliani, W., Chezzi, C., and Cassone, A. (1994). Idiotypic intravaginal vaccination to protect against candidal vaginitis by secretory, yeast killer toxin-like anti-idiotypic antibodies. J. Immunol. 152: 3175–3182.

    CAS  PubMed  Google Scholar 

  • Polonelli, L., De Bernardis, F., Conti, S., Boccanera, M., Magliani, W., Gerloni, M., Cantelli, C., and Cassone, A. (1996). Human natural yeast killer toxin-like, candidacidal antibodies. J. Immunol. 156: 1880–1885.

    CAS  PubMed  Google Scholar 

  • Polonelli, L., De Bernardis, F., Conti, S., Gerloni, M., and Cassone, A. (1997). Yeast killer toxinlike antibodies in experimental and clinical candidiasis. In Y. Shoenfeld, R.C. Kennedy, and S. Ferrone (eds), Idiotypes in Medicine: Autoimmunity, Infection and Cancer. Elsevier Science, Amsterdam, pp. 369–380.

    Google Scholar 

  • Polonelli, L., Magliani, W., Conti, S., Bracci, L., Lozzi, L., Neri, P., Adriani, D., De Bernardis, F., and Cassone, A. (2003). Therapeutic activity of an engineered synthetic killer antiidiotypic antibody fragment against experimental mucosal and systemic candidiasis. Infect. Immun. 71: 6205–6212.

    Article  CAS  PubMed  Google Scholar 

  • Rogers, T.J. and Balish, E. (1980). Immunity to Candida albicans. Microbiol. Rev. 44: 660–682.

    CAS  PubMed  Google Scholar 

  • San Millan, R., Ezkurra, P.A., Quindòs, G., Robert, R., Senet, J.M., and Pontòn J. (1996). Effect of monoclonal antibodies directed against Candida albicans cell wall antigens on the adhesion of the fungus to polystyrene. Microbiology 142: 2271–2277.

    CAS  PubMed  Google Scholar 

  • Santoni, G., Boccanera, M., Adriani, D., Lucciarini, R., Amantini, C., Morrone, S., Cassone, A., and De Bernardis, F. (2002). Immune cell-mediated protection against vaginal candidiasis: Evidence for a mayor role of vaginal CD4+ T cells and possible participation of other local lymphocyte effectors. Infect. Immun. 70: 4791–4797.

    CAS  PubMed  Google Scholar 

  • Scicchitano, R., Stanisz, A., Ernst, P.B., and Bunenstock, J. (1988). A common mucosal immune system revised. In A.J. Husband (ed.), Migration and Homing of Lymphoid Cells, Vol. 2. CRC Press, Boca Raton, FL, pp. 1–34.

    Google Scholar 

  • Sobel, J.D. (1989). Pathogenesis of Candida vulvovaginitis. In M.R. Mc Ginnis and M. Borges (eds), Current Topics in Medical Mycology. Springer-Verlag, Stuttgart, pp. 86–108.

    Google Scholar 

  • Sobel, J.D. (1992). Pathogenesis and treatment of recurrent vulvovaginal candidiasis. Clin. Infect. Dis. 14: S148–S153.

    PubMed  Google Scholar 

  • Steele, C., Ratteree, M., Harrison, R., and Fidel, P.L. Jr. (1999). Differential susceptibility to experimental vaginal candidiasis in macaque. J. Infect. Dis. 180: 802–810.

    Article  CAS  PubMed  Google Scholar 

  • Tipper, D.J. and Bostian, K.A. (1984). Double-stranded ribonucleic acid killer system in yeasts. Microbiol. Rev. 48: 125–156.

    CAS  PubMed  Google Scholar 

  • Walker, S.M. and Urbaniak, S.J. (1980). A serum-dependent defect of neutrophil function in chronic mucocutaneous candidiasis. J. Clin. Pathol. 33: 370–372.

    CAS  PubMed  Google Scholar 

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De Bernardis, F., Boccanera, M., Cassone, A. (2005). The Role of Humoral Immunity against Vaginal Candida Infection. In: Fidel, P.L., Huffnagle, G.B. (eds) Fungal Immunology. Springer, Boston, MA. https://doi.org/10.1007/0-387-25445-5_17

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