Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization

A. Torrents de la Peña; J.-P. Julien; S.W. de Taeye; F. Garces; M. Guttman; G. Ozorowski; L.K. Pritchard; A.-J. Behrens; E.P. Go; J.A. Burger; E.E. Schermer; K. Sliepen; T.J. Ketas; P. Pugach; A. Yasmeen; C.A. Cottrell; J.L. Torres; C.D. Vavourakis; M.J. van Gils; C. LaBranche; D.C. Montefiori; H. Desaire; M. Crispin; P.J. Klasse; K.K. Lee; J.P. Moore; A.B. Ward; I.A. Wilson; R.W. Sanders

doi:https://doi.org/10.1016/j.celrep.2017.07.077

Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization

A. Torrents de la Peña, J.-P. Julien, S.W. de Taeye, F. Garces, M. Guttman, G. Ozorowski, L.K. Pritchard, A.-J. Behrens, E.P. Go, J.A. Burger, E.E. Schermer, K. Sliepen, T.J. Ketas, P. Pugach, A. Yasmeen, C.A. Cottrell, J.L. Torres, C.D. Vavourakis, M.J. van Gils, C. LaBrancheD.C. Montefiori, H. Desaire, M. Crispin, P.J. Klasse, K.K. Lee, J.P. Moore, A.B. Ward, I.A. Wilson, R.W. Sanders

Research output: Contribution to journal › Article › Academic › peer-review

121 Citations (Scopus)

Abstract

The production of native-like recombinant versions of the HIV-1 envelope glycoprotein (Env) trimer requires overcoming the natural flexibility and instability of the complex. The engineered BG505 SOSIP.664 trimer mimics the structure and antigenicity of native Env. Here, we describe how the introduction of new disulfide bonds between the glycoprotein (gp)120 and gp41 subunits of SOSIP trimers of the BG505 and other genotypes improves their stability and antigenicity, reduces their conformational flexibility, and helps maintain them in the unliganded conformation. The resulting next-generation SOSIP.v5 trimers induce strong autologous tier-2 neutralizing antibody (NAb) responses in rabbits. In addition, the BG505 SOSIP.v6 trimers induced weak heterologous NAb responses against a subset of tier-2 viruses that were not elicited by the prototype BG505 SOSIP.664. These stabilization methods can be applied to trimers from multiple genotypes as components of multivalent vaccines aimed at inducing broadly NAbs (bNAbs).

Original language	English
Pages (from-to)	1805-1817
Journal	Cell reports
Volume	20
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2017.07.077
Publication status	Published - 2017

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https://doi.org/10.1016/j.celrep.2017.07.077

Cite this

Torrents de la Peña, A., Julien, J.-P., de Taeye, S. W., Garces, F., Guttman, M., Ozorowski, G., Pritchard, L. K., Behrens, A.-J., Go, E. P., Burger, J. A., Schermer, E. E., Sliepen, K., Ketas, T. J., Pugach, P., Yasmeen, A., Cottrell, C. A., Torres, J. L., Vavourakis, C. D., van Gils, M. J., ... Sanders, R. W. (2017). Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization. Cell reports, 20(8), 1805-1817. https://doi.org/10.1016/j.celrep.2017.07.077

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title = "Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization",

abstract = "The production of native-like recombinant versions of the HIV-1 envelope glycoprotein (Env) trimer requires overcoming the natural flexibility and instability of the complex. The engineered BG505 SOSIP.664 trimer mimics the structure and antigenicity of native Env. Here, we describe how the introduction of new disulfide bonds between the glycoprotein (gp)120 and gp41 subunits of SOSIP trimers of the BG505 and other genotypes improves their stability and antigenicity, reduces their conformational flexibility, and helps maintain them in the unliganded conformation. The resulting next-generation SOSIP.v5 trimers induce strong autologous tier-2 neutralizing antibody (NAb) responses in rabbits. In addition, the BG505 SOSIP.v6 trimers induced weak heterologous NAb responses against a subset of tier-2 viruses that were not elicited by the prototype BG505 SOSIP.664. These stabilization methods can be applied to trimers from multiple genotypes as components of multivalent vaccines aimed at inducing broadly NAbs (bNAbs).",

author = "{Torrents de la Pe{\~n}a}, A. and J.-P. Julien and {de Taeye}, S.W. and F. Garces and M. Guttman and G. Ozorowski and L.K. Pritchard and A.-J. Behrens and E.P. Go and J.A. Burger and E.E. Schermer and K. Sliepen and T.J. Ketas and P. Pugach and A. Yasmeen and C.A. Cottrell and J.L. Torres and C.D. Vavourakis and {van Gils}, M.J. and C. LaBranche and D.C. Montefiori and H. Desaire and M. Crispin and P.J. Klasse and K.K. Lee and J.P. Moore and A.B. Ward and I.A. Wilson and R.W. Sanders",

note = "With supplemental information",

year = "2017",

doi = "https://doi.org/10.1016/j.celrep.2017.07.077",

language = "English",

volume = "20",

pages = "1805--1817",

journal = "Cell reports",

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Torrents de la Peña, A, Julien, J-P, de Taeye, SW, Garces, F, Guttman, M, Ozorowski, G, Pritchard, LK, Behrens, A-J, Go, EP, Burger, JA, Schermer, EE, Sliepen, K, Ketas, TJ, Pugach, P, Yasmeen, A, Cottrell, CA, Torres, JL, Vavourakis, CD, van Gils, MJ, LaBranche, C, Montefiori, DC, Desaire, H, Crispin, M, Klasse, PJ, Lee, KK, Moore, JP, Ward, AB, Wilson, IA & Sanders, RW 2017, 'Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization', Cell reports, vol. 20, no. 8, pp. 1805-1817. https://doi.org/10.1016/j.celrep.2017.07.077

TY - JOUR

T1 - Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization

AU - Torrents de la Peña, A.

AU - Julien, J.-P.

AU - de Taeye, S.W.

AU - Garces, F.

AU - Guttman, M.

AU - Ozorowski, G.

AU - Pritchard, L.K.

AU - Behrens, A.-J.

AU - Go, E.P.

AU - Burger, J.A.

AU - Schermer, E.E.

AU - Sliepen, K.

AU - Ketas, T.J.

AU - Pugach, P.

AU - Yasmeen, A.

AU - Cottrell, C.A.

AU - Torres, J.L.

AU - Vavourakis, C.D.

AU - van Gils, M.J.

AU - LaBranche, C.

AU - Montefiori, D.C.

AU - Desaire, H.

AU - Crispin, M.

AU - Klasse, P.J.

AU - Lee, K.K.

AU - Moore, J.P.

AU - Ward, A.B.

AU - Wilson, I.A.

AU - Sanders, R.W.

N1 - With supplemental information

PY - 2017

Y1 - 2017

N2 - The production of native-like recombinant versions of the HIV-1 envelope glycoprotein (Env) trimer requires overcoming the natural flexibility and instability of the complex. The engineered BG505 SOSIP.664 trimer mimics the structure and antigenicity of native Env. Here, we describe how the introduction of new disulfide bonds between the glycoprotein (gp)120 and gp41 subunits of SOSIP trimers of the BG505 and other genotypes improves their stability and antigenicity, reduces their conformational flexibility, and helps maintain them in the unliganded conformation. The resulting next-generation SOSIP.v5 trimers induce strong autologous tier-2 neutralizing antibody (NAb) responses in rabbits. In addition, the BG505 SOSIP.v6 trimers induced weak heterologous NAb responses against a subset of tier-2 viruses that were not elicited by the prototype BG505 SOSIP.664. These stabilization methods can be applied to trimers from multiple genotypes as components of multivalent vaccines aimed at inducing broadly NAbs (bNAbs).

AB - The production of native-like recombinant versions of the HIV-1 envelope glycoprotein (Env) trimer requires overcoming the natural flexibility and instability of the complex. The engineered BG505 SOSIP.664 trimer mimics the structure and antigenicity of native Env. Here, we describe how the introduction of new disulfide bonds between the glycoprotein (gp)120 and gp41 subunits of SOSIP trimers of the BG505 and other genotypes improves their stability and antigenicity, reduces their conformational flexibility, and helps maintain them in the unliganded conformation. The resulting next-generation SOSIP.v5 trimers induce strong autologous tier-2 neutralizing antibody (NAb) responses in rabbits. In addition, the BG505 SOSIP.v6 trimers induced weak heterologous NAb responses against a subset of tier-2 viruses that were not elicited by the prototype BG505 SOSIP.664. These stabilization methods can be applied to trimers from multiple genotypes as components of multivalent vaccines aimed at inducing broadly NAbs (bNAbs).

U2 - https://doi.org/10.1016/j.celrep.2017.07.077

DO - https://doi.org/10.1016/j.celrep.2017.07.077

M3 - Article

C2 - 28834745

SN - 2639-1856

VL - 20

SP - 1805

EP - 1817

JO - Cell reports

JF - Cell reports

IS - 8

ER -