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. 1995 Jan 1;181(1):405–409. doi: 10.1084/jem.181.1.405

Protective and nonprotective monoclonal antibodies to Cryptococcus neoformans originating from one B cell

PMCID: PMC2191853  PMID: 7807020

Abstract

Two immunoglobulin M monoclonal antibodies (mAbs) derived from the same B cell recognize different epitopes on the capsular polysaccharide of the pathogenic yeast, Cryptococcus neoformans. Their respective epitopes are located in spatially distinct regions of the capsule. Passive administration of one mAb prolonged survival whereas the other mAb did not. The results indicate that specificity is an important determinant of antibody efficacy against C. neoformans and that somatic mutations occurring during the antibody response can affect the protective efficacy of antibodies to C. neoformans.

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Selected References

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  1. 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]
  2. 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]
  3. 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]
  4. Cherniak R., Reiss E., Slodki M. E., Plattner R. D., Blumer S. O. Structure and antigenic activity of the capsular polysaccharide of Cryptococcus neoformans serotype A. Mol Immunol. 1980 Aug;17(8):1025–1032. doi: 10.1016/0161-5890(80)90096-6. [DOI] [PubMed] [Google Scholar]
  5. Clarke S. H., Huppi K., Ruezinsky D., Staudt L., Gerhard W., Weigert M. Inter- and intraclonal diversity in the antibody response to influenza hemagglutinin. J Exp Med. 1985 Apr 1;161(4):687–704. doi: 10.1084/jem.161.4.687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DROUHET E., SEGRETAIN G. Inhibition de la migration leucocytaire in vitro par un polyoside capsulaire de Torulopsis (Cryptococcus) neoformans. Ann Inst Pasteur (Paris) 1951 Dec;81(6):674–676. [PubMed] [Google Scholar]
  7. Devi S. J., Schneerson R., Egan W., Ulrich T. J., Bryla D., Robbins J. B., Bennett J. E. Cryptococcus neoformans serotype A glucuronoxylomannan-protein conjugate vaccines: synthesis, characterization, and immunogenicity. Infect Immun. 1991 Oct;59(10):3700–3707. doi: 10.1128/iai.59.10.3700-3707.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. French D. L., Laskov R., Scharff M. D. The role of somatic hypermutation in the generation of antibody diversity. Science. 1989 Jun 9;244(4909):1152–1157. doi: 10.1126/science.2658060. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Jones K. F., Fischetti V. A. The importance of the location of antibody binding on the M6 protein for opsonization and phagocytosis of group A M6 streptococci. J Exp Med. 1988 Mar 1;167(3):1114–1123. doi: 10.1084/jem.167.3.1114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kozel T. R., Follette J. L. Opsonization of encapsulated Cryptococcus neoformans by specific anticapsular antibody. Infect Immun. 1981 Mar;31(3):978–984. doi: 10.1128/iai.31.3.978-984.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kozel T. R., Gulley W. F., Cazin J., Jr Immune response to Cryptococcus neoformans soluble polysaccharide: immunological unresponsiveness. Infect Immun. 1977 Dec;18(3):701–707. doi: 10.1128/iai.18.3.701-707.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kozel T. R., McGaw T. G. Opsonization of Cryptococcus neoformans by human immunoglobulin G: role of immunoglobulin G in phagocytosis by macrophages. Infect Immun. 1979 Jul;25(1):255–261. doi: 10.1128/iai.25.1.255-261.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. 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]
  18. 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]
  19. 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]
  20. Pettoello-Mantovani M., Casadevall A., Kollmann T. R., Rubinstein A., Goldstein H. Enhancement of HIV-1 infection by the capsular polysaccharide of Cryptococcus neoformans. Lancet. 1992 Jan 4;339(8784):21–23. doi: 10.1016/0140-6736(92)90142-p. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. 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]
  23. Wysocki L., Manser T., Gefter M. L. Somatic evolution of variable region structures during an immune response. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1847–1851. doi: 10.1073/pnas.83.6.1847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]

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