Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles

被引：34

作者：

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

Antanasijevic, Aleksandar ^{[2
]}

de Gast, Marlon ^{[1
]}

Allen, Joel D. ^{[3
]}

Bijl, Tom P. L. ^{[1
]}

Yasmeen, Anila ^{[4
]}

Ravichandran, Rashmi ^{[5
,6
]}

Burger, Judith A. ^{[1
]}

Ozorowski, Gabriel ^{[2
]}

Torres, Jonathan L. ^{[2
]}

LaBranche, Celia ^{[7
]}

Montefiori, David C. ^{[7
]}

Ringe, Rajesh P. ^{[4
,8
]}

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

Moore, John P. ^{[4
]}

Klasse, Per Johan ^{[4
]}

Crispin, Max ^{[3
]}

King, Neil P. ^{[5
,6
]}

Ward, Andrew B. ^{[2
]}

Sanders, Rogier W. ^{[1
,4
]}

机构：

[1] Univ Amsterdam, Amsterdam Infect & Immun Inst, Amsterdam UMC, Dept Med Microbiol, Amsterdam, Netherlands

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

[3] Univ Southampton, Sch Biol Sci, Southampton, Hants, England

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

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

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

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

[8] Inst Microbial Technol, Chandigarh, India

来源：

NPJ VACCINES | 2021年 / 6卷 / 01期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/s41541-021-00285-9

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The HIV-1 envelope glycoprotein trimer is poorly immunogenic because it is covered by a dense glycan shield. As a result, recombinant Env glycoproteins generally elicit inadequate antibody levels that neutralize clinically relevant, neutralization-resistant (Tier-2) HIV-1 strains. Multivalent antigen presentation on nanoparticles is an established strategy to increase vaccine-driven immune responses. However, due to nanoparticle instability in vivo, the display of non-native Env structures, and the inaccessibility of many neutralizing antibody (NAb) epitopes, the effects of nanoparticle display are generally modest for Env trimers. Here, we generate two-component self-assembling protein nanoparticles presenting twenty SOSIP trimers of the clade C Tier-2 genotype 16055. We show in a rabbit immunization study that these nanoparticles induce 60-fold higher autologous Tier-2 NAb titers than the corresponding SOSIP trimers. Epitope mapping studies reveal that the presentation of 16055 SOSIP trimers on these nanoparticle focuses antibody responses to an immunodominant apical epitope. Thus, these nanoparticles are a promising platform to improve the immunogenicity of Env trimers with apex-proximate NAb epitopes.

引用

页数：14

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