In vitro efficacy of anti-hiv immunotoxins targeted by various antibodies to the envelope protein

Seth H. Pincus, Robert L. Cole, Evan M Hersh, Douglas Lake, Yasuhiko Masuho, Paul J. Durda, Jan Mcclure

Research output: Contribution to journalArticle

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Abstract

Six different anti-HIV envelope antibodies and one irrelevant control antibody were coupled to ricin A chain and tested for their efficacy in inhibiting HIV tissue culture infections. The anti-HIV antibodies consisted of five monoclonals, three of murine and two of human origin, and one polyclonal preparation prepared by affinity purifying pooled serum antibodies from HIV-infected humans on rgp160. The binding specificity of the antibodies was defined by ELISA by using recombinant envelope proteins and synthetic peptides, and by flow cytometry on HIV-infected cells. The in vitro efficacy of the antibodies was tested by the abilities of the immunotoxins to inhibit protein synthesis in persistently infected cell lines and by their abilities to inhibit HIV production during both acute and persistent infection as measured with an HIV-specific focal immunoassay. The immunotoxins were tested against a panel of distinctly different HIV isolates. The results indicate the following: 1) A mAb to the immunodominant neutralizing loop was highly effective against homologous strains of HIV, but had no activity against heterologous HIV. 2) The efficacy of anti-gp41 mAb varied depending upon the epitope recognized and possibly the affinity of binding to gp41. 3) The polyclonal human anti-gp160 antibodies produced the immunotoxin with the broadest specificity for different HIV strains and the greatest specific activity. This is related to the polyclonal nature of the preparation rather than an increase in relative avidity of the antibody. 4) Activity of an immunotoxin is not a direct function of the binding of the antibody to the surface of infected cells. 5) The ability of an immunotoxin to halt the spread of infection through a tissue culture cell population is dependent upon the ability of the antibody to neutralize the virus as well as the activity of the toxin. Our data suggest that efficacious immunotoxins for the treatment of AIDS may be made with polyclonal anti-envelope antibodies derived from the serum of patients who have been infected with HIV or with appropriately chosen anti-gp41 antibodies.

Original languageEnglish (US)
Pages (from-to)4315-4324
Number of pages10
JournalJournal of Immunology
Volume146
Issue number12
StatePublished - Jun 15 1991

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Immunotoxins
HIV
Antibodies
HIV Antibodies
Proteins
Anti-Idiotypic Antibodies
Infection
In Vitro Techniques
Ricin
Antibody Affinity
Antibody Specificity
Serum
Immunoassay
Recombinant Proteins
Epitopes
Flow Cytometry
Acquired Immunodeficiency Syndrome
Cell Culture Techniques
Enzyme-Linked Immunosorbent Assay
Viruses

ASJC Scopus subject areas

  • Immunology

Cite this

Pincus, S. H., Cole, R. L., Hersh, E. M., Lake, D., Masuho, Y., Durda, P. J., & Mcclure, J. (1991). In vitro efficacy of anti-hiv immunotoxins targeted by various antibodies to the envelope protein. Journal of Immunology, 146(12), 4315-4324.

In vitro efficacy of anti-hiv immunotoxins targeted by various antibodies to the envelope protein. / Pincus, Seth H.; Cole, Robert L.; Hersh, Evan M; Lake, Douglas; Masuho, Yasuhiko; Durda, Paul J.; Mcclure, Jan.

In: Journal of Immunology, Vol. 146, No. 12, 15.06.1991, p. 4315-4324.

Research output: Contribution to journalArticle

Pincus, SH, Cole, RL, Hersh, EM, Lake, D, Masuho, Y, Durda, PJ & Mcclure, J 1991, 'In vitro efficacy of anti-hiv immunotoxins targeted by various antibodies to the envelope protein', Journal of Immunology, vol. 146, no. 12, pp. 4315-4324.
Pincus SH, Cole RL, Hersh EM, Lake D, Masuho Y, Durda PJ et al. In vitro efficacy of anti-hiv immunotoxins targeted by various antibodies to the envelope protein. Journal of Immunology. 1991 Jun 15;146(12):4315-4324.
Pincus, Seth H. ; Cole, Robert L. ; Hersh, Evan M ; Lake, Douglas ; Masuho, Yasuhiko ; Durda, Paul J. ; Mcclure, Jan. / In vitro efficacy of anti-hiv immunotoxins targeted by various antibodies to the envelope protein. In: Journal of Immunology. 1991 ; Vol. 146, No. 12. pp. 4315-4324.
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