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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Targeting antibody responses to the membrane proximal external region of the envelope glycoprotein of human immunodeficiency virus
PLoS ONE, Volume 7, No. 5, Article e38068, Year 2012
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Description
Although human immunodeficiency type 1 (HIV-1) infection induces strong antibody responses to the viral envelope glycoprotein (Env) only a few of these antibodies possess the capacity to neutralize a broad range of strains. The induction of such antibodies represents an important goal in the development of a preventive vaccine against the infection. Among the broadly neutralizing monoclonal antibodies discovered so far, three (2F5, Z13 and 4E10) target the short and hidden membrane proximal external region (MPER) of the gp41 transmembrane protein. Antibody responses to MPER are rarely observed in HIV-infected individuals or after immunization with Env immunogens. To initiate antibody responses to MPER in its membrane-embedded native conformation, we generated expression plasmids encoding the membrane-anchored ectodomain of gp41 with N-terminal deletions of various sizes. Following transfection of these plasmids, the MPER domains are displayed on the cell surface and incorporated into HIV virus like particles (VLP). Transfected cells displaying MPER mutants bound as efficiently to both 2F5 and 4E10 as cells transfected with a plasmid encoding full-length Env. Mice immunized with VLPs containing the MPER mutants produced MPER-specific antibodies, the levels of which could be increased by the trimerization of the displayed proteins as well as by a DNA prime-VLP boost immunization strategy. Although 2F5 competed for binding to MPER with antibodies in sera of some of the immunized mice, neutralizing activity could not be detected. Whether this is due to inefficient binding of the induced antibodies to MPER in the context of wild type Env or whether the overall MPER-specific antibody response induced by the MPER display mutants is too low to reveal neutralizing activity, remains to be determined. © 2012 Kamdem Toukam et al.
Authors & Co-Authors
Toukam, Donatien Kamdem
Germany, Bochum
Ruhr-universitat Bochum
Tenbusch, Matthias
Germany, Bochum
Ruhr-universitat Bochum
Stang, Alexander
Germany, Bochum
Ruhr-universitat Bochum
Temchura, Vladimir
Germany, Bochum
Ruhr-universitat Bochum
Bonsmann, Michael Storcksdieck Genannt
Germany, Bochum
Ruhr-universitat Bochum
Grewe, Bastian
Germany, Bochum
Ruhr-universitat Bochum
Koch, Stefanie
Germany, St Ingbert
Fraunhofer Institute for Biomedical Engineering Ibmt
Meyerhans, Andreas
Spain, Barcelona
Universitat Pompeu Fabra Barcelona
Nchinda, Godwin W.
Cameroon, Yaounde
Chantal Biya International Reference Centre for Research on Hiv/aids Prevention and Management Circb
Kaptué, Lazare Noche
Cameroon, Bangangté
Université Des Montagnes
Überla, Klaus T.
Germany, Bochum
Ruhr-universitat Bochum
Statistics
Citations: 30
Authors: 11
Affiliations: 5
Identifiers
Doi:
10.1371/journal.pone.0038068
e-ISSN:
19326203
Research Areas
Genetics And Genomics
Infectious Diseases
Maternal And Child Health