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-Structure paper
タイトル | Immunofocusing and enhancing autologous Tier-2 HIV-1 neutralization by displaying Env trimers on two-component protein nanoparticles. |
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ジャーナル・号・ページ | NPJ Vaccines, Vol. 6, Issue 1, Page 24, Year 2021 |
掲載日 | 2021年2月9日 |
著者 | Philip J M Brouwer / Aleksandar Antanasijevic / Marlon de Gast / Joel D Allen / Tom P L Bijl / Anila Yasmeen / Rashmi Ravichandran / Judith A Burger / Gabriel Ozorowski / Jonathan L Torres / Celia LaBranche / David C Montefiori / Rajesh P Ringe / Marit J van Gils / John P Moore / Per Johan Klasse / Max Crispin / Neil P King / Andrew B Ward / Rogier W Sanders / |
PubMed 要旨 | 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 ...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. |
リンク | NPJ Vaccines / PubMed:33563983 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 12.8 - 17.2 Å |
構造データ | EMDB-22714: EMDB-22715: EMDB-22716: EMDB-22717: EMDB-22718: EMDB-22719: EMDB-22720: EMDB-22721: EMDB-22722: EMDB-22723: |
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