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Targeting Antibody Responses to the Membrane Proximal External Region of the Envelope Glycoprotein of Human Immunodeficiency Virus

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 develop...

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Autores principales: Kamdem Toukam, Donatien, Tenbusch, Matthias, Stang, Alexander, Temchura, Vladimir, Storcksdieck genannt Bonsmann, Michael, Grewe, Bastian, Koch, Stefanie, Meyerhans, Andreas, Nchinda, Godwin, Kaptue, Lazare, Überla, Klaus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3364164/
https://www.ncbi.nlm.nih.gov/pubmed/22666448
http://dx.doi.org/10.1371/journal.pone.0038068
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author Kamdem Toukam, Donatien
Tenbusch, Matthias
Stang, Alexander
Temchura, Vladimir
Storcksdieck genannt Bonsmann, Michael
Grewe, Bastian
Koch, Stefanie
Meyerhans, Andreas
Nchinda, Godwin
Kaptue, Lazare
Überla, Klaus
author_facet Kamdem Toukam, Donatien
Tenbusch, Matthias
Stang, Alexander
Temchura, Vladimir
Storcksdieck genannt Bonsmann, Michael
Grewe, Bastian
Koch, Stefanie
Meyerhans, Andreas
Nchinda, Godwin
Kaptue, Lazare
Überla, Klaus
author_sort Kamdem Toukam, Donatien
collection PubMed
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.
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spelling pubmed-33641642012-06-04 Targeting Antibody Responses to the Membrane Proximal External Region of the Envelope Glycoprotein of Human Immunodeficiency Virus Kamdem Toukam, Donatien Tenbusch, Matthias Stang, Alexander Temchura, Vladimir Storcksdieck genannt Bonsmann, Michael Grewe, Bastian Koch, Stefanie Meyerhans, Andreas Nchinda, Godwin Kaptue, Lazare Überla, Klaus PLoS One Research Article 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. Public Library of Science 2012-05-30 /pmc/articles/PMC3364164/ /pubmed/22666448 http://dx.doi.org/10.1371/journal.pone.0038068 Text en Kamdem Toukam et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kamdem Toukam, Donatien
Tenbusch, Matthias
Stang, Alexander
Temchura, Vladimir
Storcksdieck genannt Bonsmann, Michael
Grewe, Bastian
Koch, Stefanie
Meyerhans, Andreas
Nchinda, Godwin
Kaptue, Lazare
Überla, Klaus
Targeting Antibody Responses to the Membrane Proximal External Region of the Envelope Glycoprotein of Human Immunodeficiency Virus
title Targeting Antibody Responses to the Membrane Proximal External Region of the Envelope Glycoprotein of Human Immunodeficiency Virus
title_full Targeting Antibody Responses to the Membrane Proximal External Region of the Envelope Glycoprotein of Human Immunodeficiency Virus
title_fullStr Targeting Antibody Responses to the Membrane Proximal External Region of the Envelope Glycoprotein of Human Immunodeficiency Virus
title_full_unstemmed Targeting Antibody Responses to the Membrane Proximal External Region of the Envelope Glycoprotein of Human Immunodeficiency Virus
title_short Targeting Antibody Responses to the Membrane Proximal External Region of the Envelope Glycoprotein of Human Immunodeficiency Virus
title_sort targeting antibody responses to the membrane proximal external region of the envelope glycoprotein of human immunodeficiency virus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3364164/
https://www.ncbi.nlm.nih.gov/pubmed/22666448
http://dx.doi.org/10.1371/journal.pone.0038068
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