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The Membrane-Proximal External Region of the Human Immunodeficiency Virus Type 1 Envelope: Dominant Site of Antibody Neutralization and Target for Vaccine Design

Marinieve Montero,^1, Nienke E. van Houten,^1,2,* Xin Wang,^1, and Jamie K. Scott^1,2*

Department of Molecular Biology and Biochemistry,¹ Faculty of Health Sciences, Simon Fraser University, 8888 University Drive, Burnaby V5A 1S6, British Columbia, Canada²

Summary: Enormous efforts have been made to produce a protective vaccine against human immunodeficiency virus type 1; there has been little success. However, the identification of broadly neutralizing antibodies against epitopes on the highly conserved membrane-proximal external region (MPER) of the gp41 envelope protein has delineated this region as an attractive vaccine target. Furthermore, emerging structural information on the MPER has provided vaccine designers with new insights for building relevant immunogens. This review describes the current state of the field regarding (i) the structure and function of the gp41 MPER; (ii) the structure and binding mechanisms of the broadly neutralizing antibodies 2F5, 4E10, and Z13; and (iii) the development of an MPER-targeting vaccine. In addition, emerging approaches to vaccine design are presented.

M.M. and N.E.V.H. contributed equally.

Present address: Division of Infectious Diseases and Hospital Ep- idemiology, University Hospital Zurich, Zurich, Switzerland.