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Journal of Virology, April 2009, p. 3617-3625, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.02631-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

In Vivo gp41 Antibodies Targeting the 2F5 Monoclonal Antibody Epitope Mediate Human Immunodeficiency Virus Type 1 Neutralization Breadth {triangledown}

Xiaoying Shen,1,2 Robert J. Parks,1,4 David C. Montefiori,1,2 Jennifer L. Kirchherr,1,4 Brandon F. Keele,6 Julie M. Decker,6 William A. Blattner,5 Feng Gao,1,4 Kent J. Weinhold,1,2,3 Charles B. Hicks,4 Michael L. Greenberg,2,{dagger} Beatrice H. Hahn,6 George M. Shaw,6 Barton F. Haynes,1,3,4 and Georgia D. Tomaras1,2,3*

Duke Human Vaccine Institute,1 Departments of Surgery,2 Immunology,3 Medicine, Duke University Medicine Center, Durham, North Carolina 27710,4 Division of Epidemiology and Prevention, Institute of Human Virology, University of Maryland, Baltimore, Maryland 21201,5 Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294-00246

Received 20 December 2008/ Accepted 27 January 2009

The broadly neutralizing human monoclonal antibodies (MAbs) 2F5 and 4E10, both targeting the highly conserved human immunodeficiency virus type 1 (HIV-1) envelope membrane proximal external region (MPER), are among the MAbs with the broadest heterologous neutralizing activity and are of considerable interest for HIV-1 vaccine development. We have identified serum antibodies from an HIV-infected subject that both were broadly neutralizing and specifically targeted MPER epitopes that overlap the 2F5 epitope. These MPER-specific antibodies were made 15 to 20 months following transmission and concomitantly with the development of autoantibodies. Our findings suggest that multiple events (i.e., genetic predisposition and HIV-1 immune dysregulation) may be required for induction of broadly reactive gp41 MPER antibodies in natural infection.

* Corresponding author. Mailing address: Duke Human Vaccine Institute, Rm. 4079, MSRBII, 106 Research Drive, Durham, NC 27710. Phone: (919) 681-5598. Fax: (919) 684-5230. E-mail: gdt{at}duke.edu

{triangledown} Published ahead of print on 4 February 2009.

{dagger} Present address: b3 Bio., Inc., Research Triangle Park, NC 27709.

Journal of Virology, April 2009, p. 3617-3625, Vol. 83, No. 8
0022-538X/09/$08.00+0     doi:10.1128/JVI.02631-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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