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. 1991 Dec;65(12):6461–6467. doi: 10.1128/jvi.65.12.6461-6467.1991

Broadly neutralizing antibodies targeted to mucin-type carbohydrate epitopes of human immunodeficiency virus.

J E Hansen 1, C Nielsen 1, M Arendrup 1, S Olofsson 1, L Mathiesen 1, J O Nielsen 1, H Clausen 1
PMCID: PMC250685  PMID: 1719230

Abstract

The cancer-related mucin-type carbohydrate neoantigen Tn was found on gp160 and gp120 of human immunodeficiency virus (HIV). Immunoglobulin G (IgG) and IgM monoclonal antibodies (MAbs) against Tn neutralized infection with cell-free virus and blocked fusion between HIV-infected and uninfected cells. This inhibition was found in infection of both lymphocytic cells and monocytoid cells. Viruses tested included six HIV-1 and five HIV-2 isolates propagated in different cells, as well as infectious plasma from AIDS patients. The antiviral effect of anti-Tn MAbs occurred by specific binding of the MAb to the virus; this binding was inhibitable by pure Tn antigen, and indications were found that this inhibition occurred at a pre-entry step. Boosting the naturally occurring low-titer anti-Tn activity may be of prophylactic value, as suggested by the in vitro neutralization found in this study.

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Selected References

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

  1. Adachi M., Hayami M., Kashiwagi N., Mizuta T., Ohta Y., Gill M. J., Matheson D. S., Tamaoki T., Shiozawa C., Hakomori S. Expression of Ley antigen in human immunodeficiency virus-infected human T cell lines and in peripheral lymphocytes of patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC). J Exp Med. 1988 Feb 1;167(2):323–331. doi: 10.1084/jem.167.2.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Akerblom L., Hinkula J., Broliden P. A., Mäkitalo B., Fridberger T., Rosen J., Villacres-Eriksson M., Morein B., Wahren B. Neutralizing cross-reactive and non-neutralizing monoclonal antibodies to HIV-1 gp120. AIDS. 1990 Oct;4(10):953–960. doi: 10.1097/00002030-199010000-00002. [DOI] [PubMed] [Google Scholar]
  3. Andrews P. W., Gönczöl E., Fenderson B. A., Holmes E. H., O'Malley G., Hakomori S., Plotkin S. Human cytomegalovirus induces stage-specific embryonic antigen 1 in differentiating human teratocarcinoma cells and fibroblasts. J Exp Med. 1989 Apr 1;169(4):1347–1359. doi: 10.1084/jem.169.4.1347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Arendrup M., Hansen J. E., Clausen H., Nielsen C., Mathiesen L. R., Nielsen J. O. Antibody to histo-blood group A antigen neutralizes HIV produced by lymphocytes from blood group A donors but not from blood group B or O donors. AIDS. 1991 Apr;5(4):441–444. doi: 10.1097/00002030-199104000-00014. [DOI] [PubMed] [Google Scholar]
  5. Berman P. W., Gregory T. J., Riddle L., Nakamura G. R., Champe M. A., Porter J. P., Wurm F. M., Hershberg R. D., Cobb E. K., Eichberg J. W. Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160. Nature. 1990 Jun 14;345(6276):622–625. doi: 10.1038/345622a0. [DOI] [PubMed] [Google Scholar]
  6. Bruyneel E. A., Debray H., De Mets M., Mareel M. M., Montreuil J. Altered glycosylation in Madin-Darby canine kidney (MDCK) cells after transformation by murine sarcoma virus. Clin Exp Metastasis. 1990 May-Jun;8(3):241–253. doi: 10.1007/BF00141255. [DOI] [PubMed] [Google Scholar]
  7. Clausen H., Levery S. B., Nudelman E., Tsuchiya S., Hakomori S. Repetitive A epitope (type 3 chain A) defined by blood group A1-specific monoclonal antibody TH-1: chemical basis of qualitative A1 and A2 distinction. Proc Natl Acad Sci U S A. 1985 Feb;82(4):1199–1203. doi: 10.1073/pnas.82.4.1199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Clavel F., Guyader M., Guétard D., Sallé M., Montagnier L., Alizon M. Molecular cloning and polymorphism of the human immune deficiency virus type 2. Nature. 1986 Dec 18;324(6098):691–695. doi: 10.1038/324691a0. [DOI] [PubMed] [Google Scholar]
  9. Desai S. M., Kalyanaraman V. S., Casey J. M., Srinivasan A., Andersen P. R., Devare S. G. Molecular cloning and primary nucleotide sequence analysis of a distinct human immunodeficiency virus isolate reveal significant divergence in its genomic sequences. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8380–8384. doi: 10.1073/pnas.83.21.8380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Franchini G., Collalti E., Arya S. K., Fenyö E. M., Biberfeld G., Zagury J. F., Kanki P. J., Wong-Staal F., Gallo R. C. Genetic analysis of a new subgroup of human and simian T-lymphotropic retroviruses: HTLV-IV, LAV-2, SBL-6669, and STLV-IIIAGM. AIDS Res Hum Retroviruses. 1987 Spring;3(1):11–17. doi: 10.1089/aid.1987.3.11. [DOI] [PubMed] [Google Scholar]
  11. Gallaher W. R. Detection of a fusion peptide sequence in the transmembrane protein of human immunodeficiency virus. Cell. 1987 Jul 31;50(3):327–328. doi: 10.1016/0092-8674(87)90485-5. [DOI] [PubMed] [Google Scholar]
  12. Gazdar A. F., Carney D. N., Bunn P. A., Russell E. K., Jaffe E. S., Schechter G. P., Guccion J. G. Mitogen requirements for the in vitro propagation of cutaneous T-cell lymphomas. Blood. 1980 Mar;55(3):409–417. [PubMed] [Google Scholar]
  13. Hansen J. E., Clausen H., Nielsen C., Teglbjaerg L. S., Hansen L. L., Nielsen C. M., Dabelsteen E., Mathiesen L., Hakomori S. I., Nielsen J. O. Inhibition of human immunodeficiency virus (HIV) infection in vitro by anticarbohydrate monoclonal antibodies: peripheral glycosylation of HIV envelope glycoprotein gp120 may be a target for virus neutralization. J Virol. 1990 Jun;64(6):2833–2840. doi: 10.1128/jvi.64.6.2833-2840.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hansen J. E., Nielsen C., Mathiesen L. R., Nielsen J. O. Involvement of lymphocyte function-associated antigen-1 (LFA-1) in HIV infection: inhibition by monoclonal antibody. Scand J Infect Dis. 1991;23(1):31–36. doi: 10.3109/00365549109023371. [DOI] [PubMed] [Google Scholar]
  15. Harada S., Koyanagi Y., Yamamoto N. Infection of HTLV-III/LAV in HTLV-I-carrying cells MT-2 and MT-4 and application in a plaque assay. Science. 1985 Aug 9;229(4713):563–566. doi: 10.1126/science.2992081. [DOI] [PubMed] [Google Scholar]
  16. Kjeldsen T., Clausen H., Hirohashi S., Ogawa T., Iijima H., Hakomori S. Preparation and characterization of monoclonal antibodies directed to the tumor-associated O-linked sialosyl-2----6 alpha-N-acetylgalactosaminyl (sialosyl-Tn) epitope. Cancer Res. 1988 Apr 15;48(8):2214–2220. [PubMed] [Google Scholar]
  17. Levy J. A., Shimabukuro J., McHugh T., Casavant C., Stites D., Oshiro L. AIDS-associated retroviruses (ARV) can productively infect other cells besides human T helper cells. Virology. 1985 Dec;147(2):441–448. doi: 10.1016/0042-6822(85)90146-1. [DOI] [PubMed] [Google Scholar]
  18. McDougal J. S., Kennedy M. S., Sligh J. M., Cort S. P., Mawle A., Nicholson J. K. Binding of HTLV-III/LAV to T4+ T cells by a complex of the 110K viral protein and the T4 molecule. Science. 1986 Jan 24;231(4736):382–385. doi: 10.1126/science.3001934. [DOI] [PubMed] [Google Scholar]
  19. Nielsen C. M., Bygbjerg I. C., Vestergaard B. F. Detection of HIV antigens in eluates from whole blood collected on filterpaper. Lancet. 1987 Mar 7;1(8532):566–567. doi: 10.1016/s0140-6736(87)90213-3. [DOI] [PubMed] [Google Scholar]
  20. Nielsen C., Petersen J. L., Nielsen C. M., Pedersen C., Mathiesen L. R., Vestergaard B. F. Isolation of HIV using T-lymphocyte 'panning': methodological aspects. J Virol Methods. 1989 Oct;26(1):105–114. doi: 10.1016/0166-0934(89)90078-5. [DOI] [PubMed] [Google Scholar]
  21. Nuti M., Teramoto Y. A., Mariani-Costantini R., Hand P. H., Colcher D., Schlom J. A monoclonal antibody (B72.3) defines patterns of distribution of a novel tumor-associated antigen in human mammary carcinoma cell populations. Int J Cancer. 1982 May 15;29(5):539–545. doi: 10.1002/ijc.2910290509. [DOI] [PubMed] [Google Scholar]
  22. Piller V., Piller F., Fukuda M. Biosynthesis of truncated O-glycans in the T cell line Jurkat. Localization of O-glycan initiation. J Biol Chem. 1990 Jun 5;265(16):9264–9271. [PubMed] [Google Scholar]
  23. Pinter A., Honnen W. J. O-linked glycosylation of retroviral envelope gene products. J Virol. 1988 Mar;62(3):1016–1021. doi: 10.1128/jvi.62.3.1016-1021.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Popovic M., Sarngadharan M. G., Read E., Gallo R. C. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984 May 4;224(4648):497–500. doi: 10.1126/science.6200935. [DOI] [PubMed] [Google Scholar]
  25. Singhal A., Fohn M., Hakomori S. Induction of alpha-N-acetylgalactosamine-O-serine/threonine (Tn) antigen-mediated cellular immune response for active immunotherapy in mice. Cancer Res. 1991 Mar 1;51(5):1406–1411. [PubMed] [Google Scholar]
  26. Skinner M. A., Langlois A. J., McDanal C. B., McDougal J. S., Bolognesi D. P., Matthews T. J. Neutralizing antibodies to an immunodominant envelope sequence do not prevent gp120 binding to CD4. J Virol. 1988 Nov;62(11):4195–4200. doi: 10.1128/jvi.62.11.4195-4200.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Springer G. F., Desai P. R., Murthy M. S., Tegtmeyer H., Scanlon E. F. Human carcinoma-associated precursor antigens of the blood group MN system and the host's immune responses to them. Prog Allergy. 1979;26:42–96. [PubMed] [Google Scholar]
  28. Stein B. S., Engleman E. G. Intracellular processing of the gp160 HIV-1 envelope precursor. Endoproteolytic cleavage occurs in a cis or medial compartment of the Golgi complex. J Biol Chem. 1990 Feb 15;265(5):2640–2649. [PubMed] [Google Scholar]
  29. Sundström C., Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer. 1976 May 15;17(5):565–577. doi: 10.1002/ijc.2910170504. [DOI] [PubMed] [Google Scholar]
  30. Thomas E. K., Weber J. N., McClure J., Clapham P. R., Singhal M. C., Shriver M. K., Weiss R. A. Neutralizing monoclonal antibodies to the AIDS virus. AIDS. 1988 Feb;2(1):25–29. doi: 10.1097/00002030-198802000-00004. [DOI] [PubMed] [Google Scholar]
  31. White J. M. Viral and cellular membrane fusion proteins. Annu Rev Physiol. 1990;52:675–697. doi: 10.1146/annurev.ph.52.030190.003331. [DOI] [PubMed] [Google Scholar]

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