Scholars@Duke publication: Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-neutralizing Epitopes.

Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-neutralizing Epitopes.

Publication , Journal Article

de Taeye, SW; Ozorowski, G; Torrents de la Peña, A; Guttman, M; Julien, J-P; van den Kerkhof, TLGM; Burger, JA; Pritchard, LK; Pugach, P; Hu, J ...

Published in: Cell

December 17, 2015

Published version (DOI) Link to item

The envelope glycoprotein trimer mediates HIV-1 entry into cells. The trimer is flexible, fluctuating between closed and more open conformations and sometimes sampling the fully open, CD4-bound form. We hypothesized that conformational flexibility and transient exposure of non-neutralizing, immunodominant epitopes could hinder the induction of broadly neutralizing antibodies (bNAbs). We therefore modified soluble Env trimers to stabilize their closed, ground states. The trimer variants were indeed stabilized in the closed conformation, with a reduced ability to undergo receptor-induced conformational changes and a decreased exposure of non-neutralizing V3-directed antibody epitopes. In rabbits, the stabilized trimers induced similar autologous Tier-1B or Tier-2 NAb titers to those elicited by the corresponding wild-type trimers but lower levels of V3-directed Tier-1A NAbs. Stabilized, closed trimers might therefore be useful components of vaccines aimed at inducing bNAbs.

Duke Scholars

Author David Charles Montefiori Surgery, Surgical Sciences

Author Celia Crane LaBranche Surgery, Surgical Sciences

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Published In

Cell

DOI

10.1016/j.cell.2015.11.056

EISSN

1097-4172

Publication Date

December 17, 2015

Volume

163

Issue

Start / End Page

1702 / 1715

Location

United States

Related Subject Headings

env Gene Products, Human Immunodeficiency Virus
Rabbits
Protein Conformation
Mutagenesis
Models, Molecular
Immunoglobulin G
Hydrophobic and Hydrophilic Interactions
HIV-1
HIV Envelope Protein gp41
Epitopes

Citation

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Chicago

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NLM

de Taeye, S. W., Ozorowski, G., Torrents de la Peña, A., Guttman, M., Julien, J.-P., van den Kerkhof, T. L. G. M., … Sanders, R. W. (2015). Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-neutralizing Epitopes. Cell, 163(7), 1702–1715. https://doi.org/10.1016/j.cell.2015.11.056

Taeye, Steven W. de, Gabriel Ozorowski, Alba Torrents de la Peña, Miklos Guttman, Jean-Philippe Julien, Tom L. G. M. van den Kerkhof, Judith A. Burger, et al. “Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-neutralizing Epitopes.” Cell 163, no. 7 (December 17, 2015): 1702–15. https://doi.org/10.1016/j.cell.2015.11.056.

de Taeye SW, Ozorowski G, Torrents de la Peña A, Guttman M, Julien J-P, van den Kerkhof TLGM, et al. Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-neutralizing Epitopes. Cell. 2015 Dec 17;163(7):1702–15.

de Taeye, Steven W., et al. “Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-neutralizing Epitopes.” Cell, vol. 163, no. 7, Dec. 2015, pp. 1702–15. Pubmed, doi:10.1016/j.cell.2015.11.056.

de Taeye SW, Ozorowski G, Torrents de la Peña A, Guttman M, Julien J-P, van den Kerkhof TLGM, Burger JA, Pritchard LK, Pugach P, Yasmeen A, Crampton J, Hu J, Bontjer I, Torres JL, Arendt H, DeStefano J, Koff WC, Schuitemaker H, Eggink D, Berkhout B, Dean H, LaBranche C, Crotty S, Crispin M, Montefiori DC, Klasse PJ, Lee KK, Moore JP, Wilson IA, Ward AB, Sanders RW. Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-neutralizing Epitopes. Cell. 2015 Dec 17;163(7):1702–1715.

Published In

Cell

DOI

10.1016/j.cell.2015.11.056

EISSN

1097-4172

Publication Date

December 17, 2015

Volume

163

Issue

Start / End Page

1702 / 1715

Location

United States

Related Subject Headings

env Gene Products, Human Immunodeficiency Virus
Rabbits
Protein Conformation
Mutagenesis
Models, Molecular
Immunoglobulin G
Hydrophobic and Hydrophilic Interactions
HIV-1
HIV Envelope Protein gp41
Epitopes