Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles.
Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles.
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DOI：
10.1038/s41541-021-00285-9
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发表时间：
2021-02-09
期刊：
影响因子：
9.2
通讯作者：
Sanders RW
中科院分区：
文献类型：
--
作者：
Brouwer PJM;Antanasijevic A;de Gast M;Allen JD;Bijl TPL;Yasmeen A;Ravichandran R;Burger JA;Ozorowski G;Torres JL;LaBranche C;Montefiori DC;Ringe RP;van Gils MJ;Moore JP;Klasse PJ;Crispin M;King NP;Ward AB;Sanders RW
HIV-1包膜糖蛋白三聚体免疫原性差，因为它被致密的聚糖盾覆盖。因此，重组Env糖蛋白通常引起中和临床相关的中和抗性（Tier-2）HIV-1毒株的抗体水平不足。纳米颗粒上的多价抗原呈递是增加疫苗驱动的免疫应答的既定策略。然而，由于纳米颗粒在体内的不稳定性、非天然Env结构的展示以及许多中和抗体（NAb）表位的不可接近性，纳米颗粒展示的效果对于Env三聚体通常是适度的。在这里，我们产生了两个组件的自组装蛋白质纳米粒子呈现二十SOSIP三聚体的进化枝C层-2基因型16055。我们在兔免疫研究中显示，这些纳米颗粒诱导的自体Tier-2 NAb滴度比相应的SOSIP三聚体高60倍。表位作图研究表明，这些纳米颗粒上的16055 SOSIP三聚体的呈递将抗体应答集中于免疫显性顶端表位。因此，这些纳米颗粒是一个有前途的平台，以提高与顶端接近NAb表位的Env三聚体的免疫原性。
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.
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影响因子：
8.8
作者：
Torrents de la Peña A;Julien JP;de Taeye SW;Garces F;Guttman M;Ozorowski G;Pritchard LK;Behrens AJ;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
通讯作者：
Sanders RW
影响因子：
8
作者：
Kelly, Hannah G.;Tan, Hyon-Xhi;Wheatley, Adam K.
通讯作者：
Wheatley, Adam K.
影响因子：
6.7
作者：
Antanasijevic, Aleksandar;Ueda, George;Ward, Andrew B.
通讯作者：
Ward, Andrew B.
影响因子：
64.5
作者：
de Taeye SW;Ozorowski G;Torrents de la Peña A;Guttman M;Julien JP;van den Kerkhof TL;Burger JA;Pritchard LK;Pugach P;Yasmeen A;Crampton J;Hu J;Bontjer I;Torres JL;Arendt H;DeStefano J;Koff WC;Schuitemaker H;Eggink D;Berkhout B;Dean H;LaBranche C;Crotty S;Crispin M;Montefiori DC;Klasse PJ;Lee KK;Moore JP;Wilson IA;Ward AB;Sanders RW
通讯作者：
Sanders RW
影响因子：
32.4
作者：
Guenaga J;Garces F;de Val N;Stanfield RL;Dubrovskaya V;Higgins B;Carrette B;Ward AB;Wilson IA;Wyatt RT
通讯作者：
Wyatt RT