Enhancing and shaping the immunogenicity of native-like HIV-1 envelope trimers with a two-component protein nanoparticle

被引：149

作者：

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

Antanasijevic, Aleksandar ^{[2
]}

Berndsen, Zachary ^{[2
]}

Yasmeen, Anila ^{[3
]}

Fiala, Brooke ^{[4
,5
]}

Bijl, Tom Pl ^{[1
]}

Bontjer, Ilja ^{[1
]}

Bale, Jacob B. ^{[4
,5
,11
]}

Sheffler, William ^{[4
,5
]}

Allen, Joel D. ^{[6
,7
]}

Schorcht, Anna ^{[1
]}

Burgers, Judith A. ^{[1
]}

Camacho, Miguel ^{[1
]}

Ellis, Daniel ^{[4
,5
]}

Cottrell, Christopher A. ^{[2
]}

Behrens, Anna-Janina ^{[8
,12
]}

Catalano, Marco ^{[1
]}

Del Moral-Sanchez, Ivan ^{[1
]}

Ketas, Thomas J. ^{[3
]}

LaBranche, Celia ^{[9
]}

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

Sliepen, Kwinten ^{[1
]}

Stewart, Lance J. ^{[4
,5
]}

Crispin, Max ^{[6
,7
,8
]}

Montefiori, David C. ^{[9
]}

Baker, David ^{[4
,5
,10
]}

Moore, John P. ^{[3
]}

Klasse, Per Johan ^{[3
]}

Ward, Andrew B. ^{[2
]}

King, Neil P. ^{[4
,5
]}

Sanders, Rogier W. ^{[1
]}

机构：

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

[2] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA

[3] Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10065 USA

[4] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[5] Univ Washington, Inst Prot Design, Seattle, WA 98195 USA

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

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

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

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

[10] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98105 USA

[11] Arzeda Corp, Seattle, WA 98119 USA

[12] New England Biolabs Inc, Ipswich, MA 01938 USA

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

美国国家卫生研究院;

关键词：

ENV TRIMERS; NEUTRALIZING ANTIBODIES; ACCURATE DESIGN; VACCINE; TARGET; VALIDATION; PARTICLES; RESPONSES; SYSTEM; CELLS;

D O I：

10.1038/s41467-019-12080-1

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：

The development of native-like HIV-1 envelope (Env) trimer antigens has enabled the induction of neutralizing antibody (NAb) responses against neutralization-resistant HIV-1 strains in animal models. However, NAb responses are relatively weak and narrow in specificity. Displaying antigens in a multivalent fashion on nanoparticles (NPs) is an established strategy to increase their immunogenicity. Here we present the design and characterization of two-component protein NPs displaying 20 stabilized SOSIP trimers from various HIV-1 strains. The two-component nature permits the incorporation of exclusively well-folded, native-like Env trimers into NPs that self-assemble in vitro with high efficiency. Immunization studies show that the NPs are particularly efficacious as priming immunogens, improve the quality of the Ab response over a conventional one-component nanoparticle system, and are most effective when SOSIP trimers with an apex-proximate neutralizing epitope are displayed. Their ability to enhance and shape the immunogenicity of SOSIP trimers make these NPs a promising immunogen platform.

引用

页数：17

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