Distinction of human immunodeficiency virus type 1 neutralization and infection enhancement by human monoclonal antibodies to glycoprotein 120

Akira Takeda, James E. Robinson, David D. Ho, Christine Debouck, Nancy Haigwood, Francis A. Ennis

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

There is increasing evidence that sera from HIV-1-infected individuals contain antibodies that enhance infection by HIV-1 in vitro. Previous work has demonstrated that complement receptors on T lymphoid cells and Fc receptors for IgG (FcγR) on monocytic cells are required for enhanced infection by antibody-complexed HIV-1. Characterization of such infection-enhancing antibodies is essential because immunogenic epitopes which induce enhancing antibodies should be excluded from HIV-1 vaccines. This study was conducted to identify enhancing antibodies involved in Fc R-mediated enhancement of HIV-1 infection employing IgG human monoclonal antibodies (HMAbs) reactive against gp120 of HIV-1, which were produced by B cell lines derived from an HIV-1-infected individual. A potent neutralizing HMAb N70-1.5e did not enhance infection by HIV-1 (IIIB and MN strains), whereas HMAb N70-2.3a mediated enhancement of HIV-1 infection, but had little neutralizing activity. A competition radio immunoassay demonstrated that the two antibodies bind to distinct epitopes. These results indicated that enhancing and neutralizing antibodies can be induced by different epitopes on gp120, suggesting the potential for development of safe vaccines against HIV-1 by exclusion of immunogenic epitopes for enhancing antibodies. We made attempts to identify the epitope on gp120 that is recognized by the enhancing antibody N70-2.3a by using recombinant HIV-1 proteins and found that the antibody binds to a conformational site of nonvariable sequences in the carboxyl half (aa 272-509) of gp120.

Original languageEnglish (US)
Pages (from-to)1952-1957
Number of pages6
JournalJournal of Clinical Investigation
Volume89
Issue number6
StatePublished - 1992
Externally publishedYes

Fingerprint

HIV-1
Glycoproteins
Monoclonal Antibodies
Blocking Antibodies
Infection
Epitopes
Antibodies
HIV Infections
Immunoglobulin G
HIV Envelope Protein gp120
Human Immunodeficiency Virus Proteins
Complement Receptors
AIDS Vaccines
Fc Receptors
T-Cell Antigen Receptor
Neutralizing Antibodies
Radio
Immunoassay
Recombinant Proteins
B-Lymphocytes

Keywords

  • Epitope
  • HIV-1
  • Infection enhancement
  • Monoclonal antibodies
  • Neutralization

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Distinction of human immunodeficiency virus type 1 neutralization and infection enhancement by human monoclonal antibodies to glycoprotein 120. / Takeda, Akira; Robinson, James E.; Ho, David D.; Debouck, Christine; Haigwood, Nancy; Ennis, Francis A.

In: Journal of Clinical Investigation, Vol. 89, No. 6, 1992, p. 1952-1957.

Research output: Contribution to journalArticle

Takeda, Akira ; Robinson, James E. ; Ho, David D. ; Debouck, Christine ; Haigwood, Nancy ; Ennis, Francis A. / Distinction of human immunodeficiency virus type 1 neutralization and infection enhancement by human monoclonal antibodies to glycoprotein 120. In: Journal of Clinical Investigation. 1992 ; Vol. 89, No. 6. pp. 1952-1957.
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