1887

Abstract

A panel of human immunodeficiency virus type 2 (HIV-2)-neutralizing, recombinant Fab fragments was generated by using the phage display technique. The combinatorial library was derived from an asymptomatic, HIV-2-seropositive individual and constructed on the surface of filamentous phage by using the pComb3 phagemid vector and then screened against native HIV-2 envelope glycoprotein (gp125). Ten of 30 Fab fragments generated displayed strong reactivity in an ELISA and were therefore selected for further study. Six of these possessed neutralizing capacity, with titres varying from 20 to 80 against the homologous HIV-2 strain, and one also had a weak neutralizing capacity against a heterologous HIV-2 isolate, K135. Sequencing of the heavy chain CDR3 regions showed that the gp125-specific Fabs represented individual clones. These reagents may be useful for studies on the conformational structures of the HIV-2 envelope antigens and their immunogenicity, which may help in vaccine design. Furthermore, the cloned Fab genes may be transformed into whole IgG for eukaryotic expression, and as such used for therapeutic and immunoprophylactic studies in HIV-2-infected macaques and, possibly, for human immunoprophylaxis against HIV-2.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-80-8-1987
1999-08-01
2019-10-15
Loading full text...

Full text loading...

/deliver/fulltext/jgv/80/8/0801987a.html?itemId=/content/journal/jgv/10.1099/0022-1317-80-8-1987&mimeType=html&fmt=ahah

References

  1. Albert, J., Bredberg-Rådén, U., Chiodi, F., Böttiger, B., Fenyö, E.-M., Norrby, E. & Biberfeld, G. ( 1987; ). A new human retrovirus isolate of West African origin (SBL-6669) and its relationship to HTLV-IV, LAV-II, and HTLV-IIIB. AIDS Research and Human Retroviruses 3, 3-10.[CrossRef]
    [Google Scholar]
  2. Albert, J., Stålhandske, P., Marquina, S., Karis, J., Fouchier, R. A., Norrby, E. & Chiodi, F. ( 1996; ). Biological phenotype of HIV type 2 isolates correlates with V3 genotype. AIDS Research and Human Retroviruses 12, 821-828.[CrossRef]
    [Google Scholar]
  3. Barbas, C. F., III & Lerner, R. A. (1991). Combinatorial libraries on the surface of phage (Phabs): rapid selection of antigen-specific Fabs. Methods (supplement to Methods in Enzymology) 2, 119–124.
  4. Barbas, C. F.III, Kang, A. S., Lerner, R. A. & Benkovic, S. J. ( 1991; ). Assembly of combinatorial antibody libraries on phage surfaces: the gene III site. Proceedings of the National Academy of Sciences, USA 88, 7978-7982.[CrossRef]
    [Google Scholar]
  5. Barbas, C. F.III, Hu, D., Dunlop, N., Sawyer, L., Cababa, D., Hendry, R. M., Nara, P. L. & Burton, D. R. ( 1994; ). In vitro evolution of a neutralizing human antibody to human immunodeficiency virus type 1 to enhance affinity and broaden strain cross-reactivity. Proceedings of the National Academy of Sciences, USA 91, 3809-3813.[CrossRef]
    [Google Scholar]
  6. Björling, E., Broliden, K., Bernardi, D., Utter, G., Thorstensson, R., Chiodi, F. & Norrby, E. ( 1991; ). Hyperimmune antisera against synthetic peptides representing the glycoprotein of human immunodeficiency virus type 2 can mediate neutralization and antibody-dependent cytotoxic activity. Proceedings of the National Academy of Sciences, USA 88, 6082-6086.[CrossRef]
    [Google Scholar]
  7. Björling, E., Chiodi, F., Utter, G. & Norrby, E. ( 1994; ). Two neutralizing domains in the V3 region in the envelope glycoprotein gp125 of HIV type 2. Journal of Immunology 152, 1952-1959.
    [Google Scholar]
  8. Böttiger, B., Karlsson, A., Andreasson, P. Å., Naucler, A., Mendes Costa, C. & Biberfeld, G. ( 1989; ). Cross-neutralizing antibodies against HIV-1 (HTLV-IIIB and HTLV-IIIRF) and HIV-2 (SBL-6669 and a new isolate SBL-K135). AIDS Research and Human Retroviruses 5, 525-533.[CrossRef]
    [Google Scholar]
  9. Böttiger, B., Karlsson, A., Andreasson, P. Å., Naucler, A., Mendes Costa, C., Norrby, E. & Biberfeld, G. ( 1990; ). Envelope cross-reactivity between human immunodeficiency virus types 1 and 2 detected by different serological methods: correlation between cross-neutralization and reactivity against the main neutralizing site. Journal of Virology 64, 3492-3499.
    [Google Scholar]
  10. Burton, D. R., Barbas, C. F.III, Persson, M. A. A., Koenig, S., Chanock, R. M. & Lerner, R. A. ( 1991; ). A large array of human monoclonal antibodies to type 1 human immunodeficiency virus from combinatorial libraries of asymptomatic seropositive individuals. Proceedings of the National Academy of Sciences, USA 88, 10134-10137.[CrossRef]
    [Google Scholar]
  11. Cavacini, L. A., Emes, C. L., Power, J., Underdahl, J., Goldstein, R., Mayer, K. & Posner, M. R. ( 1993; ). Loss of serum antibodies to a conformational epitope of HIV-1/gp120 identified by a human monoclonal antibody is associated with disease progression. Journal of Acquired Immune Deficiency Syndromes 6, 1093-1102.
    [Google Scholar]
  12. Chomczynski, P. & Sacchi, N. ( 1987; ). Single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chlorophorm extraction. Analytical Biochemistry 162, 156-159.
    [Google Scholar]
  13. Clavel, F., Guetard, D., Brun-Vezinet, F., Chamaret, S., Rey, M. A., Santos-Ferreira, M. O., Laurent, A. G., Dauguet, C., Katlama, C., Rouzioux, C., Klatzmann, D., Champalimaud, J. L. & Montagnier, L. ( 1986; ). Isolation of a new human retrovirus from West African patients with AIDS. Science 233, 343-346.[CrossRef]
    [Google Scholar]
  14. Collet, T. A., Roben, P., O’Kennedy, R., Barbas, C. F.III, Burton, D. R. & Lerner, R. A. ( 1992; ). A binary plasmid system for shuffling combinatorial antibody libraries. Proceedings of the National Academy of Sciences, USA 89, 10026-10030.[CrossRef]
    [Google Scholar]
  15. Hultman, T., Ståhl, S., Hornes, E. & Uhlén, M. ( 1989; ). Direct solid phase sequencing of genomic and plasmid DNA using magnetic beads as solid support. Nucleic Acids Research 17, 4937-4946.[CrossRef]
    [Google Scholar]
  16. Kang, A. S., Burton, D. R. & Lerner, R. A. (1991a). Combinatorial immunoglobulin libraries in phage lambda. Methods (supplement to Methods in Enzymology) 2, 111–118.
  17. Kang, C. Y., Nara, P., Chamat, S., Caralli, V., Ryskamp, T., Haigwood, N., Newman, R. & Kohler, H. ( 1991b; ). Evidence for non-V3-specific neutralizing antibodies that interfere with gp120/CD4 binding in human immunodeficiency virus 1-infected humans. Proceedings of the National Academy of Sciences, USA 88, 6171-6175.[CrossRef]
    [Google Scholar]
  18. Kanki, P. J., M’Boup, S., Ricard, D., Barin, F., Denis, F., Boye, C., Sangare, L., Travers, K., Albaum, M., Marlink, R., Romet-Lemonne, J.-L. & Essex, M. ( 1987; ). Human T-lymphotropic virus type 4 and the human immunodeficiency virus in West Africa. Science 236, 827-831.[CrossRef]
    [Google Scholar]
  19. Kent, K. & Björling, E. ( 1997; ). B-cell epitopes in the envelope glycoproteins of HIV-2 and SIV. In HIV Molecular Immunology Database 1996, pp. IV-1-IV-17. Edited by B. T. M. Korber, B. D. Walker, J. P. Moore & G. Myers. Los Alamos, NM: Los Alamos National Laboratory.
  20. Kent, K. A., Powell, C., Corcoran, T., Jenkins, A., Almond, N., Jones, I., Robinson, J. & Stott, E. J. (1993). Characterization of neutralizing epitopes of simian immunodeficiency virus envelope using monoclonal antibodies. In Proceedings of the Huitieme Colloque des Cent Gardes, pp. 167–172.
  21. Lum, L. G., Burns, E., Janson, M. M., Martin, P. J., Giddings, B. R., Seigneuret, M. C., Noges, J. E. & Galoforo, S. C. ( 1990; ). IgG anti-tetanus toxoid antibody synthesis by human bone marrow. I. Two distinct populations of marrow B cells and functional differences between marrow and peripheral blood B cells. Journal of Clinical Immunology 10, 255-264.[CrossRef]
    [Google Scholar]
  22. McKeating, J. A., Thali, M., Furman, C., Karwowska, S., Gorny, M. K., Cordell, J., Zolla-Pazner, S., Sodroski, J. & Weiss, R. A. ( 1992; ). Amino acid residues of the human immunodeficiency virus type 1 gp120 critical for the binding of rat and human neutralizing antibodies that block the gp120–sCD4 interaction. Virology 190, 134-142.[CrossRef]
    [Google Scholar]
  23. McKnight, Á., Shotton, C., Cordell, J., Jones, I., Simmons, G. & Clapham, P. R. ( 1996; ). Location, exposure, and conservation of neutralizing and nonneutralizing epitopes on human immunodeficiency virus type 2 SU glycoprotein. Journal of Virology 70, 4598-4606.
    [Google Scholar]
  24. Matsushita, S., Matsumi, S., Yoshimura, K., Morikita, T., Murakami, T. & Takatsuki, K. ( 1995; ). Neutralizing monoclonal antibodies against human immunodeficiency virus type 2 gp120. Journal of Virology 69, 3333-3340.
    [Google Scholar]
  25. Moore, J. P. & Ho, D. D. ( 1995; ). HIV-1 neutralization: the consequences of viral adaptation to growth on transformed T cells. AIDS 9 (Suppl. A), S117–S136.
    [Google Scholar]
  26. Nakamura, G. R., Byrn, R., Rosenthal, K., Porter, J. P., Hobbs, M. R., Riddle, L., Eastman, D. J., Dowbenko, D., Gregory, T., Fendly, B. M. & Berman, P. W. ( 1992; ). Monoclonal antibodies to the extracellular domain of HIV-1IIIB gp160 that neutralize infectivity, block binding to CD4, and react with diverse isolates. AIDS Research and Human Retroviruses 8, 1875-1885.[CrossRef]
    [Google Scholar]
  27. Norrby, E., Putkonen, P., Böttiger, B., Utter, G. & Biberfeld, G. ( 1991; ). Comparison of linear antigenic sites in the envelope proteins of human immunodeficiency virus (HIV) type 2 and type 1. AIDS Research and Human Retroviruses 7, 279-285.[CrossRef]
    [Google Scholar]
  28. Parren, P. W. & Burton, D. R. ( 1997; ). Antibodies against HIV-1 from phage display libraries: mapping of an immune response and progress towards antiviral immunotherapy. Chemical Immunology 65, 18-56.
    [Google Scholar]
  29. Posner, M. R., Cavacini, L. A., Emes, C. L., Power, J. & Byrn, R. ( 1993; ). Neutralization of HIV-1 by F105, a human monoclonal antibody to the CD4 binding site of gp120. Journal of Acquired Immune Deficiency Syndromes 6, 7-14.
    [Google Scholar]
  30. Ranki, A., Weiss, S. H., Valle, S. L., Antonen, J. & Krohn, K. J. E. ( 1987; ). Neutralizing antibodies in HIV (HTLV-III) infection: correlation with clinical outcome and antibody response against different viral proteins. Clinical and Experimental Immunology 69, 231-239.
    [Google Scholar]
  31. Rath, S., Stanley, C. M. & Steward, M. W. ( 1988; ). An inhibition enzyme immunoassay for estimating relative antibody affinity and affinity heterogeneity. Journal of Immunological Methods 106, 245-249.[CrossRef]
    [Google Scholar]
  32. Sambrook, J., Fritsch, E. F. & Maniatis, T. (1989). Molecular Cloning: A Laboratory Manual, 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  33. Samuelsson, A., Chiodi, F., Öhman, P., Putkonen, P., Norrby, E. & Persson, M. A. A. ( 1995; ). Chimeric macaque/human Fab molecules neutralize simian immunodeficiency virus. Virology 207, 495-502.[CrossRef]
    [Google Scholar]
  34. Samuelsson, A., Yari, F., Hinkula, J., Ersoy, O., Norrby, E. & Persson, M. A. A. ( 1996; ). Human antibodies from phage libraries: neutralizing activity against human immunodeficiency virus type 1 equally improved after expression as Fab and IgG in mammalian cells. European Journal of Immunology 26, 3029-3034.[CrossRef]
    [Google Scholar]
  35. Steimer, K. S., Scandella, C. J., Skiles, P. V. & Haigwood, N. L. ( 1991; ). Neutralization of divergent HIV-1 isolates by conformation-dependent human antibodies to Gp120. Science 254, 105-108.[CrossRef]
    [Google Scholar]
  36. Thali, M., Furman, C., Ho, D. D., Robinson, J., Tilley, S., Pinter, A. & Sodroski, J. ( 1992; ). Discontinuous, conserved neutralization epitopes overlapping the CD4-binding region of human immunodeficiency virus type 1 gp120 envelope glycoprotein. Journal of Virology 66, 5635-5641.
    [Google Scholar]
  37. Thorstensson, R., Walther, L., Putkonen, P., Albert, J. & Biberfeld, G. ( 1991; ). A capture enzyme immunoassay for detection of HIV-2/SIV antigen. Journal of Acquired Immune Deficiency Syndromes 4, 374-379.
    [Google Scholar]
  38. Weiss, R. A., Clapham, P. R., Weber, J., Cheingsong-Popov, R., Dalgleish, A., Carne, C. A., Weller, I. V. & Tedder, R. S. ( 1985; ). Neutralization of human T-lymphotropic virus type III by sera of AIDS and AIDS-risk patients. Nature 316, 69-72.[CrossRef]
    [Google Scholar]
  39. Weiss, R. A., Clapham, P. R., Weber, J. N., Whitby, D., Tedder, R. S., O’Connor, T., Chamaret, S. & Montagnier, L. ( 1988; ). HIV-2 antisera cross-neutralize HIV-1. AIDS 2, 95-100.[CrossRef]
    [Google Scholar]
  40. Williamson, R. A., Burioni, R., Sanna, P. P., Partridge, L. J., Barbas, C. F.III & Burton, D. R. ( 1993; ). Human monoclonal antibodies against a plethora of viral pathogens from single combinatorial libraries. Proceedings of the National Academy of Sciences, USA 90, 4141-4145.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-80-8-1987
Loading
/content/journal/jgv/10.1099/0022-1317-80-8-1987
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error