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

被引：123

作者：

de la Pena, Alba Torrents ^{[1
]}

Julien, Jean-Philippe ^{[2
,3
,11
,12
,13
]}

de Taeye, Steven W. ^{[1
]}

Garces, Fernando ^{[2
,3
,14
]}

Guttman, Miklos ^{[4
]}

Ozorowski, Gabriel ^{[2
,3
]}

Pritchard, Laura K. ^{[5
]}

Behrens, Anna-Janina ^{[5
]}

Go, Eden P. ^{[6
]}

Burger, Judith A. ^{[1
]}

Schermer, Edith E. ^{[1
]}

Sliepen, Kwinten ^{[1
]}

Ketas, Thomas J. ^{[7
]}

Pugach, Pavel ^{[7
]}

Yasmeen, Anila ^{[7
]}

Cottrell, Christopher A. ^{[2
,3
]}

Torres, Jonathan L. ^{[2
,3
]}

Vavourakis, Charlotte D. ^{[8
]}

van Gils, Marit J. ^{[1
]}

LaBranche, Celia ^{[9
]}

Montefiori, David C. ^{[9
]}

Desaire, Heather ^{[6
]}

Crispin, Max ^{[5
]}

Klasse, Per Johan ^{[7
]}

Lee, Kelly K. ^{[4
]}

Moore, John P. ^{[7
]}

Ward, Andrew B. ^{[2
,3
]}

Wilson, Ian A. ^{[2
,3
,10
]}

Sanders, Rogier W. ^{[1
,7
]}

机构：

[1] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands

[2] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, Scripps CHAVI ID, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA

[3] Scripps Res Inst, CAVD, La Jolla, CA 92037 USA

[4] Univ Washington, Dept Med Chem, Seattle, WA 98195 USA

[5] Univ Oxford, Oxford Glycobiol Inst, Dept Biochem, Oxford OX1 3QU, England

[6] Univ Kansas, Dept Chem, Lawrence, KS 66047 USA

[7] Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA

[8] Univ Amsterdam, Inst Biodivers & Ecosyst Dynam, Dept Freshwater & Marine Ecol, Microbial Syst Ecol, NL-1098 XH Amsterdam, Netherlands

[9] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA

[10] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

[11] Hosp Sick Children, Program Mol Med, Res Inst, Toronto, ON M5G 0A4, Canada

[12] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada

[13] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada

[14] Amgen Inc, Dept Therapeut Discovery, Thousand Oaks, CA 92320 USA

来源：

CELL REPORTS | 2017年 / 20卷 / 08期

基金：

欧洲研究理事会;

关键词：

BROADLY NEUTRALIZING ANTIBODIES; CRYO-EM STRUCTURE; GLYCOPROTEIN COMPLEX; DISULFIDE BONDS; GLYCOSYLATION; TARGET;

D O I：

10.1016/j.celrep.2017.07.077

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 heterologousNAbresponses 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).

引用

页码：1805 / 1817

页数：13

共 50 条

[41] Comparative Immunogenicity of Evolved V1V2-Deleted HIV-1 Envelope Glycoprotein Trimers
Bontjer, Ilja
Melchers, Mark
Tong, Tommy
van Montfort, Thijs
Eggink, Dirk
Montefiori, David
Olson, William C.
Moore, John P.
Binley, James M.
Berkhout, Ben
Sanders, Rogier W.
PLOS ONE, 2013, 8 (06):
[42] Antigenicity and Immunogenicity of HIV-1 Envelope Trimers Complexed to a Small-Molecule Viral Entry Inhibitor
Alam, S. Munir
Cronin, Kenneth
Parks, Robert
Anasti, Kara
Ding, Haitao
Go, Eden P.
Desaire, Heather
Eaton, Amanda
Montefiori, David
Sodroski, Joseph
Kappes, John
Haynes, Barton F.
Saunders, Kevin O.
JOURNAL OF VIROLOGY, 2020, 94 (21)
[43] Design and crystal structure of a native-like HIV-1 envelope trimer that engages multiple broadly neutralizing antibody precursors in vivo
Medina-Ramirez, Max
Garces, Fernando
Escolano, Amelia
Skog, Patrick
de Taeye, Steven W.
Del Moral-Sanchez, Ivan
McGuire, Andrew T.
Yasmeen, Anila
Behrens, Anna-Janina
Ozorowski, Gabriel
van den Kerkhof, Tom L. G. M.
Freund, Natalia T.
Dosenovic, Pia
Hua, Yuanzi
Gitlin, Alexander D.
Cupo, Albert
van der Woude, Patricia
Golabek, Michael
Sliepen, Kwinten
Blane, Tanya
Kootstra, Neeltje
van Breemen, Marielle J.
Pritchard, Laura K.
Stanfield, Robyn L.
Crispin, Max
Ward, Andrew B.
Stamatatos, Leonidas
Klasse, Per Johan
Moore, John P.
Nemazee, David
Nussenzweig, Michel C.
Wilson, Ian A.
Sanders, Rogier W.
JOURNAL OF EXPERIMENTAL MEDICINE, 2017, 214 (09): : 2573 - 2590
[44] Stable, uncleaved HIV-1 envelope glycoprotein gp140 forms a tightly folded trimer with a native-like structure
Kovacs, James M.
Noeldeke, Erik
Ha, Heather Jiwon
Peng, Hanqin
Rits-Volloch, Sophia
Harrison, Stephen C.
Chen, Bing
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (52) : 18542 - 18547
[45] Immunogenicity of HIV-1 envelope glycoprotein oligomers
Forsell, Mattias N. E.
Schief, William R.
Wyatt, Richard T.
CURRENT OPINION IN HIV AND AIDS, 2009, 4 (05) : 380 - 387
[46] Stoichiometric Analyses of Soluble CD4 to Native-like HIV-1 Envelope by Single-Molecule Fluorescence Spectroscopy
Agrawal, Parul
DeVico, Anthony L.
Foulke, James S., Jr.
Lewis, George K.
Pazgier, Marzena
Ray, Krishanu
CELL REPORTS, 2019, 29 (01): : 176 - +
[47] Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles
Linling He
Natalia de Val
Charles D. Morris
Nemil Vora
Therese C. Thinnes
Leopold Kong
Parisa Azadnia
Devin Sok
Bin Zhou
Dennis R. Burton
Ian A Wilson
David Nemazee
Andrew B. Ward
Jiang Zhu
Nature Communications, 7
[48] HIV-1-neutralizing antibody induced by simian adenovirus- and poxvirus MVA-vectored BG505 native-like envelope trimers
Capucci, Silvia
Wee, Edmund G.
Schiffner, Torben
LaBranche, Celia C.
Borthwick, Nicola
Cupo, Albert
Dodd, Jonathan
Dean, Hansi
Sattentau, Quentin
Montefiori, David
Klasse, Per J.
Sanders, Rogier W.
Moore, John P.
Hanke, Tomas
PLOS ONE, 2017, 12 (08):
[49] Stabilized HIV-1 envelope glycoprotein trimers for vaccine use
Medina-Ramirez, Max
Sanders, Rogier W.
Sattentau, Quentin J.
CURRENT OPINION IN HIV AND AIDS, 2017, 12 (03) : 241 - 249
[50] Presenting native-like trimeric HIV-1 antigens with self-assembling nanoparticles
He, Linling
de Val, Natalia
Morris, Charles D.
Vora, Nemil
Thinnes, Therese C.
Kong, Leopold
Azadnia, Parisa
Sok, Devin
Zhou, Bin
Burton, Dennis R.
Wilson, Ian A.
Nemazee, David
Ward, Andrew B.
Zhu, Jiang
NATURE COMMUNICATIONS, 2016, 7

← 1 2 3 4 5 →