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-Structure paper
タイトル | Antigen spacing on protein nanoparticles influences antibody responses to vaccination. |
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ジャーナル・号・ページ | Cell Rep, Vol. 42, Issue 12, Page 113552, Year 2023 |
掲載日 | 2023年12月26日 |
著者 | Daniel Ellis / Annie Dosey / Seyhan Boyoglu-Barnum / Young-Jun Park / Rebecca Gillespie / Hubza Syeda / Geoffrey B Hutchinson / Yaroslav Tsybovsky / Michael Murphy / Deleah Pettie / Nick Matheson / Sidney Chan / George Ueda / Jorge A Fallas / Lauren Carter / Barney S Graham / David Veesler / Masaru Kanekiyo / Neil P King / |
PubMed 要旨 | Immunogen design approaches aim to control the specificity and quality of antibody responses elicited by next-generation vaccines. Here, we use computational protein design to generate a nanoparticle ...Immunogen design approaches aim to control the specificity and quality of antibody responses elicited by next-generation vaccines. Here, we use computational protein design to generate a nanoparticle vaccine platform based on the receptor-binding domain (RBD) of influenza hemagglutinin (HA) that enables precise control of antigen conformation and spacing. HA RBDs are presented as either monomers or native-like closed trimers that are connected to the underlying nanoparticle by a rigid linker that is modularly extended to precisely control antigen spacing. Nanoparticle immunogens with decreased spacing between trimeric RBDs elicit antibodies with improved hemagglutination inhibition and neutralization potency as well as binding breadth across diverse H1 HAs. Our "trihead" nanoparticle immunogen platform provides insights into anti-HA immunity, establishes antigen spacing as an important parameter in structure-based vaccine design, and embodies several design features that could be used in next-generation vaccines against influenza and other viruses. |
リンク | Cell Rep / PubMed:38096058 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.7 - 6.8 Å |
構造データ | EMDB-42481: I53_dn5 nanoparticle displaying the trimeric HA heads with heptad domain, TH-1heptad-I53_dn5 EMDB-42482, PDB-8ur5: EMDB-42483: I53_dn5 nanoparticle displaying the trimeric HA heads with heptad domain, TH-2heptad-I53_dn5 EMDB-42485: I53_dn5 nanoparticle displaying the trimeric HA heads with heptad domain, TH-6heptad-I53_dn5 EMDB-42486, PDB-8ur7: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRAL PROTEIN / Influenza virus / Hemagglutinin nanoparticle vaccine / Structural Genomics / Seattle Structural Genomics Center for Infectious Disease / SSGCID |