Neutralization of divergent human immunodeficiency virus type 1 variants and primary isolates by IAM-41-2F5, an anti-gp41 human monoclonal antibody.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 91 ·No. 8 ·1994-04-12 ·Pages 3348-52

Conley AJ, Kessler JA, Boots LJ, Tung JS, Arnold BA, Keller PM, Shaw AR, Emini EA

Abstract

The antiviral characteristics of monoclonal antibody IAM-41-2F5 (2F5) were determined in cell culture. The antibody had been previously shown to bind a specific sequence, ELDKWA, within the external domain of the gp41 envelope glycoprotein human immunodeficiency virus type 1 (HIV-1). Selection by 2F5 of recombinant phage from an epitope library confirmed the identification of the antibody's binding determinant. The antibody was found to be capable of neutralizing a broad range of lymphoid cell culture-adapted HIV-1 variants as well as HIV-1 primary isolates. Sequence analysis of the latter showed that neutralization was related to the presence of the antibody binding site. From kinetic measurements using an epitope-containing peptide or gp41, the half-time of dissociation for 2F5 was determined to be 122 min for the peptide and 156 min for gp41. The region of gp41 expressing this sequence exhibits greater conservation among HIV-1 isolates than do the variable domains of gp120.

MeSH Terms

Amino Acid Sequence Antibodies, Monoclonal/immunology Antibody Affinity Antibody Specificity Base Sequence DNA Primers/chemistry Epitopes Genes, env HIV Antibodies/immunology HIV Envelope Protein gp41/immunology HIV-1/immunology Humans Molecular Sequence Data Neutralization Tests Peptides/immunology Sequence Alignment Sequence Homology, Amino Acid

Chemicals

Antibodies, Monoclonal DNA Primers Epitopes HIV Antibodies HIV Envelope Protein gp41 Peptides

Authors & Affiliations

8 authors, click to expand affiliations / ORCID

Conley A J

Department of Antiviral Research, Merck Research Laboratories, West Point, PA 19486.

Kessler J A

Boots L J

Tung J S

Arnold B A

Keller P M

Shaw A R

Emini E A

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Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.91.8.3348

Published

1994-04-12

Pages

3348-52

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC43574

Subset

Databases

GENBANK

U06721, U06722, U06723, U06724, U06725, U06726, U06727, U06728, U06729, U06730, U06731, U06732, U06733, U06734, U06735, U06736, U06737, U06738, U06739, U06740, U06741, U06742, U06743

External Links

PubMed source DOI: 10.1073/pnas.91.8.3348 PMC Full Text View journal details

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Neutralization of divergent human immunodeficiency virus type 1 variants and primary isolates by IAM-41-2F5, an anti-gp41 human monoclonal antibody.

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