Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1995 Sep;63(9):3353–3359. doi: 10.1128/iai.63.9.3353-3359.1995

Variable efficacy of passive antibody administration against diverse Cryptococcus neoformans strains.

J Mukherjee 1, M D Scharff 1, A Casadevall 1
PMCID: PMC173461  PMID: 7642262

Abstract

The efficacy of monoclonal antibody (MAb 2H1) against diverse strains of Cryptococcus neoformans was studied in a murine model of intravenous infection. For six of eight strains, administration of MAb prior to infection prolonged survival of mice. For two strains, 371 and SB4A, administration of MAb prior to infection did not prolong survival in multiple experiments with inocula ranging from 10(2) to 10(6) yeast cells per mouse. Mice infected with strains 371 and SB4A had fewer CFU than non-MAb-treated controls, but the CFU reduction was not sufficient to affect survival. Serum glucuronoxylomannan (GXM) levels varied for the different C. neoformans strains. For mice that did not receive MAb 2H1, there was a positive correlation between lung fungal burden and serum GXM levels. MAb 2H1-treated mice had significantly reduced serum GXM levels. The results indicate that the efficacy of MAb 2H1 administration in prolonging survival and/or reducing organ CFU varies with the C. neoformans strain.

Full Text

The Full Text of this article is available as a PDF (215.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abrahams I. Further studies on acquired resistance to murine cryptococcosis: enhancing effect of Bordetella pertussis. J Immunol. 1966 Mar;96(3):525–529. [PubMed] [Google Scholar]
  2. Brueske C. H. Proteolytic activity of a clinical isolate of Cryptococcus neoformans. J Clin Microbiol. 1986 Mar;23(3):631–633. doi: 10.1128/jcm.23.3.631-633.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Casadevall A., Freundlich L. F., Marsh L., Scharff M. D. Extensive allelic variation in Cryptococcus neoformans. J Clin Microbiol. 1992 May;30(5):1080–1084. doi: 10.1128/jcm.30.5.1080-1084.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Casadevall A., Mukherjee J., Devi S. J., Schneerson R., Robbins J. B., Scharff M. D. Antibodies elicited by a Cryptococcus neoformans-tetanus toxoid conjugate vaccine have the same specificity as those elicited in infection. J Infect Dis. 1992 Jun;165(6):1086–1093. doi: 10.1093/infdis/165.6.1086. [DOI] [PubMed] [Google Scholar]
  5. Casadevall A., Mukherjee J., Scharff M. D. Monoclonal antibody based ELISAs for cryptococcal polysaccharide. J Immunol Methods. 1992 Sep 18;154(1):27–35. doi: 10.1016/0022-1759(92)90209-c. [DOI] [PubMed] [Google Scholar]
  6. Casadevall A., Scharff M. D. The mouse antibody response to infection with Cryptococcus neoformans: VH and VL usage in polysaccharide binding antibodies. J Exp Med. 1991 Jul 1;174(1):151–160. doi: 10.1084/jem.174.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Casadevall A., Spitzer E. D., Webb D., Rinaldi M. G. Susceptibilities of serial Cryptococcus neoformans isolates from patients with recurrent cryptococcal meningitis to amphotericin B and fluconazole. Antimicrob Agents Chemother. 1993 Jun;37(6):1383–1386. doi: 10.1128/aac.37.6.1383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cherniak R., Morris L. C., Anderson B. C., Meyer S. A. Facilitated isolation, purification, and analysis of glucuronoxylomannan of Cryptococcus neoformans. Infect Immun. 1991 Jan;59(1):59–64. doi: 10.1128/iai.59.1.59-64.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cherniak R., Morris L. C., Belay T., Spitzer E. D., Casadevall A. Variation in the structure of glucuronoxylomannan in isolates from patients with recurrent cryptococcal meningitis. Infect Immun. 1995 May;63(5):1899–1905. doi: 10.1128/iai.63.5.1899-1905.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cleare W., Mukherjee S., Spitzer E. D., Casadevall A. Prevalence in Cryptococcus neoformans strains of a polysaccharide epitope which can elicit protective antibodies. Clin Diagn Lab Immunol. 1994 Nov;1(6):737–740. doi: 10.1128/cdli.1.6.737-740.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dromer F., Charreire J., Contrepois A., Carbon C., Yeni P. Protection of mice against experimental cryptococcosis by anti-Cryptococcus neoformans monoclonal antibody. Infect Immun. 1987 Mar;55(3):749–752. doi: 10.1128/iai.55.3.749-752.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dromer F., Charreire J. Improved amphotericin B activity by a monoclonal anti-Cryptococcus neoformans antibody: study during murine cryptococcosis and mechanisms of action. J Infect Dis. 1991 May;163(5):1114–1120. doi: 10.1093/infdis/163.5.1114. [DOI] [PubMed] [Google Scholar]
  13. Dromer F., Perronne C., Barge J., Vilde J. L., Yeni P. Role of IgG and complement component C5 in the initial course of experimental cryptococcosis. Clin Exp Immunol. 1989 Dec;78(3):412–417. [PMC free article] [PubMed] [Google Scholar]
  14. GADEBUSCH H. H. Passive immunization against Cryptococcus neoformans. Proc Soc Exp Biol Med. 1958 Jul;98(3):611–614. doi: 10.3181/00379727-98-24123. [DOI] [PubMed] [Google Scholar]
  15. Ghannoum M. A., Spellberg B. J., Ibrahim A. S., Ritchie J. A., Currie B., Spitzer E. D., Edwards J. E., Jr, Casadevall A. Sterol composition of Cryptococcus neoformans in the presence and absence of fluconazole. Antimicrob Agents Chemother. 1994 Sep;38(9):2029–2033. doi: 10.1128/aac.38.9.2029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Goldman D. L., Lee S. C., Casadevall A. Tissue localization of Cryptococcus neoformans glucuronoxylomannan in the presence and absence of specific antibody. Infect Immun. 1995 Sep;63(9):3448–3453. doi: 10.1128/iai.63.9.3448-3453.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Goldman D., Lee S. C., Casadevall A. Pathogenesis of pulmonary Cryptococcus neoformans infection in the rat. Infect Immun. 1994 Nov;62(11):4755–4761. doi: 10.1128/iai.62.11.4755-4761.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Goren M. B. Experimental murine cryptococcosis: effect of hyperimmunization to capsular polysaccharide. J Immunol. 1967 May;98(5):914–922. [PubMed] [Google Scholar]
  19. Graybill J. R., Hague M., Drutz D. J. Passive immunization in murine cryptococcosis. Sabouraudia. 1981 Dec;19(4):237–244. doi: 10.1080/00362178185380411. [DOI] [PubMed] [Google Scholar]
  20. Grosse G., Mishra S. K., Staib F. Selective involvement of the brain in experimental murine cryptococcosis. II. Histopathological observations. Zentralbl Bakteriol Orig A. 1975 Sep;233(1):106–122. [PubMed] [Google Scholar]
  21. HASENCLEVER H. F., MITCHELL W. O. Virulence and growth rates of Cryptococcus neoformans in mice. Ann N Y Acad Sci. 1960 Aug 27;89:156–162. doi: 10.1111/j.1749-6632.1960.tb20138.x. [DOI] [PubMed] [Google Scholar]
  22. Hill J. O. CD4+ T cells cause multinucleated giant cells to form around Cryptococcus neoformans and confine the yeast within the primary site of infection in the respiratory tract. J Exp Med. 1992 Jun 1;175(6):1685–1695. doi: 10.1084/jem.175.6.1685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Huffnagle G. B., Yates J. L., Lipscomb M. F. Immunity to a pulmonary Cryptococcus neoformans infection requires both CD4+ and CD8+ T cells. J Exp Med. 1991 Apr 1;173(4):793–800. doi: 10.1084/jem.173.4.793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kozel T. R., Gotschlich E. C. The capsule of cryptococcus neoformans passively inhibits phagocytosis of the yeast by macrophages. J Immunol. 1982 Oct;129(4):1675–1680. [PubMed] [Google Scholar]
  25. Kozel T. R., Pfrommer G. S. Activation of the complement system by Cryptococcus neoformans leads to binding of iC3b to the yeast. Infect Immun. 1986 Apr;52(1):1–5. doi: 10.1128/iai.52.1.1-5.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kwon-Chung K. J., Polacheck I., Bennett J. E. Improved diagnostic medium for separation of Cryptococcus neoformans var. neoformans (serotypes A and D) and Cryptococcus neoformans var. gattii (serotypes B and C). J Clin Microbiol. 1982 Mar;15(3):535–537. doi: 10.1128/jcm.15.3.535-537.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lehrer R. I., Lichtenstein A. K., Ganz T. Defensins: antimicrobial and cytotoxic peptides of mammalian cells. Annu Rev Immunol. 1993;11:105–128. doi: 10.1146/annurev.iy.11.040193.000541. [DOI] [PubMed] [Google Scholar]
  28. Levitz S. M., DiBenedetto D. J. Paradoxical role of capsule in murine bronchoalveolar macrophage-mediated killing of Cryptococcus neoformans. J Immunol. 1989 Jan 15;142(2):659–665. [PubMed] [Google Scholar]
  29. Louria D. B., Kaminski T. Passively-acquired immunity in experimental cryptococcosis. Sabouraudia. 1965 Jun;4(2):80–84. doi: 10.1080/00362176685190211. [DOI] [PubMed] [Google Scholar]
  30. Miller M. F., Mitchell T. G., Storkus W. J., Dawson J. R. Human natural killer cells do not inhibit growth of Cryptococcus neoformans in the absence of antibody. Infect Immun. 1990 Mar;58(3):639–645. doi: 10.1128/iai.58.3.639-645.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Monga D. P., Kumar R., Mohapatra L. N., Malaviya A. N. Experimental cryptococcosis in normal and B-cell-deficient mice. Infect Immun. 1979 Oct;26(1):1–3. doi: 10.1128/iai.26.1.1-3.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Mozaffarian N., Berman J. W., Casadevall A. Immune complexes increase nitric oxide production by interferon-gamma- stimulated murine macrophage-like J774.16 cells. J Leukoc Biol. 1995 Apr;57(4):657–662. doi: 10.1002/jlb.57.4.657. [DOI] [PubMed] [Google Scholar]
  33. Mukherjee J., Casadevall A., Scharff M. D. Molecular characterization of the humoral responses to Cryptococcus neoformans infection and glucuronoxylomannan-tetanus toxoid conjugate immunization. J Exp Med. 1993 Apr 1;177(4):1105–1116. doi: 10.1084/jem.177.4.1105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Mukherjee J., Nussbaum G., Scharff M. D., Casadevall A. Protective and nonprotective monoclonal antibodies to Cryptococcus neoformans originating from one B cell. J Exp Med. 1995 Jan 1;181(1):405–409. doi: 10.1084/jem.181.1.405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Mukherjee J., Pirofski L. A., Scharff M. D., Casadevall A. Antibody-mediated protection in mice with lethal intracerebral Cryptococcus neoformans infection. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3636–3640. doi: 10.1073/pnas.90.8.3636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Mukherjee J., Scharff M. D., Casadevall A. Cryptococcus neoformans infection can elicit protective antibodies in mice. Can J Microbiol. 1994 Oct;40(10):888–892. doi: 10.1139/m94-141. [DOI] [PubMed] [Google Scholar]
  37. Mukherjee J., Scharff M. D., Casadevall A. Protective murine monoclonal antibodies to Cryptococcus neoformans. Infect Immun. 1992 Nov;60(11):4534–4541. doi: 10.1128/iai.60.11.4534-4541.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Mukherjee J., Zuckier L. S., Scharff M. D., Casadevall A. Therapeutic efficacy of monoclonal antibodies to Cryptococcus neoformans glucuronoxylomannan alone and in combination with amphotericin B. Antimicrob Agents Chemother. 1994 Mar;38(3):580–587. doi: 10.1128/aac.38.3.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Mukherjee S., Lee S. C., Casadevall A. Antibodies to Cryptococcus neoformans glucuronoxylomannan enhance antifungal activity of murine macrophages. Infect Immun. 1995 Feb;63(2):573–579. doi: 10.1128/iai.63.2.573-579.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Mukherjee S., Lee S., Mukherjee J., Scharff M. D., Casadevall A. Monoclonal antibodies to Cryptococcus neoformans capsular polysaccharide modify the course of intravenous infection in mice. Infect Immun. 1994 Mar;62(3):1079–1088. doi: 10.1128/iai.62.3.1079-1088.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Nathan C. Nitric oxide as a secretory product of mammalian cells. FASEB J. 1992 Sep;6(12):3051–3064. [PubMed] [Google Scholar]
  42. Perfect J. R., Lang S. D., Durack D. T. Influence of agglutinating antibody in experimental cryptococcal meningitis. Br J Exp Pathol. 1981 Dec;62(6):595–599. [PMC free article] [PubMed] [Google Scholar]
  43. Rhodes J. C., Wicker L. S., Urba W. J. Genetic control of susceptibility to Cryptococcus neoformans in mice. Infect Immun. 1980 Aug;29(2):494–499. doi: 10.1128/iai.29.2.494-499.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Sanford J. E., Lupan D. M., Schlageter A. M., Kozel T. R. Passive immunization against Cryptococcus neoformans with an isotype-switch family of monoclonal antibodies reactive with cryptococcal polysaccharide. Infect Immun. 1990 Jun;58(6):1919–1923. doi: 10.1128/iai.58.6.1919-1923.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Schlageter A. M., Kozel T. R. Opsonization of Cryptococcus neoformans by a family of isotype-switch variant antibodies specific for the capsular polysaccharide. Infect Immun. 1990 Jun;58(6):1914–1918. doi: 10.1128/iai.58.6.1914-1918.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Small J. M., Mitchell T. G. Strain variation in antiphagocytic activity of capsular polysaccharides from Cryptococcus neoformans serotype A. Infect Immun. 1989 Dec;57(12):3751–3756. doi: 10.1128/iai.57.12.3751-3756.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Spira G., Bargellesi A., Teillaud J. L., Scharff M. D. The identification of monoclonal class switch variants by sib selection and an ELISA assay. J Immunol Methods. 1984 Nov 30;74(2):307–315. doi: 10.1016/0022-1759(84)90298-9. [DOI] [PubMed] [Google Scholar]
  48. Spiropulu C., Eppard R. A., Otteson E., Kozel T. R. Antigenic variation within serotypes of Cryptococcus neoformans detected by monoclonal antibodies specific for the capsular polysaccharide. Infect Immun. 1989 Oct;57(10):3240–3242. doi: 10.1128/iai.57.10.3240-3242.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Spitzer E. D., Keath E. J., Travis S. J., Painter A. A., Kobayashi G. S., Medoff G. Temperature-sensitive variants of Histoplasma capsulatum isolated from patients with acquired immunodeficiency syndrome. J Infect Dis. 1990 Jul;162(1):258–261. doi: 10.1093/infdis/162.1.258. [DOI] [PubMed] [Google Scholar]
  50. Spitzer E. D., Spitzer S. G., Freundlich L. F., Casadevall A. Persistence of initial infection in recurrent Cryptococcus neoformans meningitis. Lancet. 1993 Mar 6;341(8845):595–596. doi: 10.1016/0140-6736(93)90354-j. [DOI] [PubMed] [Google Scholar]
  51. Vanbreuseghem R. White mice sensitivity to Cryptococcus neoformans. Production of resistance against a cerebral inoculation. Ann Soc Belges Med Trop Parasitol Mycol. 1967;47(4):281–294. [PubMed] [Google Scholar]
  52. Young B. J., Kozel T. R. Effects of strain variation, serotype, and structural modification on kinetics for activation and binding of C3 to Cryptococcus neoformans. Infect Immun. 1993 Jul;61(7):2966–2972. doi: 10.1128/iai.61.7.2966-2972.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Yuan R., Casadevall A., Spira G., Scharff M. D. Isotype switching from IgG3 to IgG1 converts a nonprotective murine antibody to Cryptococcus neoformans into a protective antibody. J Immunol. 1995 Feb 15;154(4):1810–1816. [PubMed] [Google Scholar]
  54. Zebedee S. L., Koduri R. K., Mukherjee J., Mukherjee S., Lee S., Sauer D. F., Scharff M. D., Casadevall A. Mouse-human immunoglobulin G1 chimeric antibodies with activities against Cryptococcus neoformans. Antimicrob Agents Chemother. 1994 Jul;38(7):1507–1514. doi: 10.1128/aac.38.7.1507. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES