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Journal of Virology, October 2003, p. 11125-11138, Vol. 77, No. 20
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.20.11125-11138.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Microarray Profiling of Antibody Responses against Simian-Human Immunodeficiency Virus: Postchallenge Convergence of Reactivities Independent of Host Histocompatibility Type and Vaccine Regimen

Henry E. Neuman de Vegvar,^1,2,3 Rama Rao Amara,⁴ Lawrence Steinman,² Paul J. Utz,¹ Harriet L. Robinson,⁴ and William H. Robinson^1,2,3*

Division of Immunology and Rheumatology, Department of Medicine,¹ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305,² Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304,³ Emory Vaccine Center and Yerkes Regional Primate Research Center, Emory University, Atlanta, Georgia 30322⁴

Received 14 April 2003/ Accepted 21 July 2003

We developed antigen microarrays to profile the breadth, strength, and kinetics of epitope-specific antiviral antibody responses in vaccine trials with a simian-human immunodeficiency virus (SHIV) model for human immunodeficiency virus (HIV) infection. These arrays contained 430 distinct proteins and overlapping peptides spanning the SHIV proteome. In macaques vaccinated with three different DNA and/or recombinant modified vaccinia virus Ankara (rMVA) vaccines encoding Gag-Pol or Gag-Pol-Env, these arrays distinguished vaccinated from challenged macaques, identified three novel viral epitopes, and predicted survival. Following viral challenge, anti-SHIV antibody responses ultimately converged to target eight immunodominant B-cell regions in Env regardless of vaccine regimen, host histocompatibility type, and divergent T-cell specificities. After challenge, responses to nonimmunodominant epitopes were transient, while responses to dominant epitopes were gained. These data suggest that the functional diversity of anti-SHIV B-cell responses is highly limited in the presence of persisting antigen.

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* Corresponding author. Mailing address: Geriatric Research, Education and Clinical Center, VA Palo Alto Health Care System, 3801 Miranda Ave., Palo Alto, CA 94304. Phone: (650) 849-1207. Fax: (650) 849-1208. E-mail: wrobins{at}stanford.edu.

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Journal of Virology, October 2003, p. 11125-11138, Vol. 77, No. 20
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.20.11125-11138.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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