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Journal of Virology, December 2004, p. 13232-13252, Vol. 78, No. 23
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.23.13232-13252.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Comprehensive Cross-Clade Neutralization Analysis of a Panel of Anti-Human Immunodeficiency Virus Type 1 Monoclonal Antibodies

James M. Binley,1,{dagger} Terri Wrin,2 Bette Korber,3 Michael B. Zwick,1 Meng Wang,1 Colombe Chappey,2 Gabriela Stiegler,4 Renate Kunert,4 Susan Zolla-Pazner,5 Hermann Katinger,4 Christos J. Petropoulos,2 and Dennis R. Burton1*

Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla,1 ViroLogic Inc., South San Francisco, California,2 Theory Division, Los Alamos National Laboratory, Los Alamos, and The Santa Fe Institute, Santa Fe, New Mexico,3 Institute of Applied Microbiology, University of Agricultural Sciences, Muthgasse, Vienna, Austria,4 Department of Pathology, New York University Medical Center, and Research Center for AIDS and HIV Infection, VA Medical Center, New York, New York5

Received 3 May 2004/ Accepted 9 July 2004

Broadly neutralizing monoclonal antibodies (MAbs) are potentially important tools in human immunodeficiency virus type 1 (HIV-1) vaccine design. A few rare MAbs have been intensively studied, but we still have a limited appreciation of their neutralization breadth. Using a pseudovirus assay, we evaluated MAbs from clade B-infected donors and a clade B HIV+ plasma against 93 viruses from diverse backgrounds. Anti-gp120 MAbs exhibited greater activity against clade B than non-B viruses, whereas anti-gp41 MAbs exhibited broad interclade activity. Unexpectedly, MAb 4E10 (directed against the C terminus of the gp41 ectodomain) neutralized all 90 viruses with moderate potency. MAb 2F5 (directed against an epitope adjacent to that of 4E10) neutralized 67% of isolates, but none from clade C. Anti-gp120 MAb b12 (directed against an epitope overlapping the CD4 binding site) neutralized 50% of viruses, including some from almost every clade. 2G12 (directed against a high-mannose epitope on gp120) neutralized 41% of the viruses, but none from clades C or E. MAbs to the gp120 V3 loop, including 447-52D, neutralized a subset of clade B viruses (up to 45%) but infrequently neutralized other clades (≤7%). MAbs b6 (directed against the CD4 binding site) and X5 (directed against a CD4-induced epitope of gp120) neutralized only sensitive primary clade B viruses. The HIV+ plasma neutralized 70% of the viruses, including some from all major clades. Further analysis revealed five neutralizing immunotypes that were somewhat associated with clades. As well as the significance for vaccine design, our data have implications for passive-immunization studies in countries where clade C viruses are common, given that only MAbs b12 and 4E10 were effective against viruses from this clade.

* Corresponding author. Mailing address: IMM2, Department of Immunology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-9298. Fax: (858) 784-8360. E-mail: burton{at}scripps.edu.

{dagger} Present address: Torrey Pines Institute for Molecular Studies, San Diego, CA 92121.

Journal of Virology, December 2004, p. 13232-13252, Vol. 78, No. 23
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.23.13232-13252.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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