Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence

被引：107

作者：

Sliepen, Kwinten ^{[1
]}

Han, Byung Woo ^{[2
,3
,4
]}

Bontjer, Ilja ^{[1
]}

Mooij, Petra ^{[5
]}

Garces, Fernando ^{[2
,3
,13
]}

Behrens, Anna-Janina ^{[6
,14
]}

Rantalainen, Kimmo ^{[2
,3
]}

Kumar, Sonu ^{[2
,3
]}

Sarkar, Anita ^{[2
,3
]}

Brouwer, Philip J. M. ^{[1
]}

Hua, Yuanzi ^{[2
,3
]}

Tolazzi, Monica ^{[7
]}

Schermer, Edith ^{[1
]}

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

Ozorowski, Gabriel ^{[2
,3
]}

van der Woude, Patricia ^{[1
]}

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

van Breemen, Marielle J. ^{[1
]}

Camacho-Sanchez, Juan Miguel ^{[1
]}

Burger, Judith A. ^{[1
]}

Medina-Ramirez, Max ^{[1
]}

Gonzalez, Nuria ^{[8
]}

Alcami, Jose ^{[8
]}

LaBranche, Celia ^{[9
]}

Scarlatti, Gabriella ^{[7
]}

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

Crispin, Max ^{[6
,15
,16
]}

Montefiori, David C. ^{[9
]}

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

Koopman, Gerrit ^{[5
]}

Moore, John P. ^{[10
]}

Shattock, Robin J. ^{[11
]}

Bogers, Willy M. ^{[5
]}

Wilson, Ian A. ^{[2
,3
,12
]}

Sanders, Rogier W. ^{[1
,10
]}

机构：

[1] Univ Amsterdam, Amsterdam UMC, Amsterdam Infect & Immun Inst, Dept Med Microbiol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands

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

[3] Scripps Res Inst, Collaborat AIDS Vaccine Discovery CAVD, La Jolla, CA 92037 USA

[4] Seoul Natl Univ, Pharmaceut Sci Res Inst, Coll Pharm, Seoul 08826, South Korea

[5] Biomed Primate Res Ctr, Dept Virol, NL-2280 GH Rijswijk, Netherlands

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

[7] IRCCS San Raffaele Sci Inst, Viral Evolut & Transmiss Unit, Div Immunol Transplantat & Infect Dis, I-20132 Milan, Italy

[8] Inst Salud Carlos III, AIDS Immunopathol Unit, Madrid 28220, Spain

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

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

[11] Imperial Coll London, Dept Med, Div Infect Dis, Virol Sect, Norfolk Pl, London W2 1PG, England

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

[13] Amgen Inc, Amgen Res, Dept Therapeut Discovery, 1 Amgen Ctr Dr, Thousand Oaks, CA 91320 USA

[14] New England Biolabs Inc, 240 Cty Rd, Ipswich, MA 01938 USA

[15] Univ Southampton, Ctr Biol Sci, Southampton SO17 1BJ, Hants, England

[16] Univ Southampton, Inst Life Sci, Southampton SO17 1BJ, Hants, England

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

美国国家卫生研究院; 新加坡国家研究基金会;

关键词：

CRYO-EM STRUCTURE; GLYCOPROTEIN COMPLEX; GERMLINE PRECURSORS; GLYCAN SHIELD; SUBTYPE-B; VACCINE; DESIGN; ENV; ANTIBODIES; CELL;

D O I：

10.1038/s41467-019-10262-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Stabilized HIV-1 envelope glycoproteins (Env) that resemble the native Env are utilized in vaccination strategies aimed at inducing broadly neutralizing antibodies (bNAbs). To limit the exposure of rare isolate-specific antigenic residues/determinants we generated a SOSIP trimer based on a consensus sequence of all HIV-1 group M isolates (ConM). The ConM trimer displays the epitopes of most known bNAbs and several germline bNAb precursors. The crystal structure of the ConM trimer at 3.9 angstrom resolution resembles that of the native Env trimer and its antigenic surface displays few rare residues. The ConM trimer elicits strong NAb responses against the autologous virus in rabbits and macaques that are significantly enhanced when it is presented on ferritin nanoparticles. The dominant NAb specificity is directed against an epitope at or close to the trimer apex. Immunogens based on consensus sequences might have utility in engineering vaccines against HIV-1 and other viruses.

引用

页数：16

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