5TR8

Crystal structure of vaccine-elicited pan- influenza H1N1 neutralizing murine antibody 441D6.

5TR8 の概要

• エントリーDOI: 10.2210/pdb5tr8/pdb
• 分子名称: 441D6 Fab Light chain, 441D6 Fab Heavy chain, NICKEL (II) ION, ... (4 entities in total)
• 機能のキーワード: nanoparticle, ferritin, immune system, antibody
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47691.37

構造登録者

Joyce, M.G.,Kanekiyo, M.,Mascola, J.R.,Graham, B.S.,Kwong, P.D. (登録日: 2016-10-25, 公開日: 2018-05-09, 最終更新日: 2024-11-20)

主引用文献

Kanekiyo, M.,Joyce, M.G.,Gillespie, R.A.,Gallagher, J.R.,Andrews, S.F.,Yassine, H.M.,Wheatley, A.K.,Fisher, B.E.,Ambrozak, D.R.,Creanga, A.,Leung, K.,Yang, E.S.,Boyoglu-Barnum, S.,Georgiev, I.S.,Tsybovsky, Y.,Prabhakaran, M.S.,Andersen, H.,Kong, W.P.,Baxa, U.,Zephir, K.L.,Ledgerwood, J.E.,Koup, R.A.,Kwong, P.D.,Harris, A.K.,McDermott, A.B.,Mascola, J.R.,Graham, B.S.
Mosaic nanoparticle display of diverse influenza virus hemagglutinins elicits broad B cell responses.
Nat.Immunol., 20:362-372, 2019

PubMed Abstract: The present vaccine against influenza virus has the inevitable risk of antigenic discordance between the vaccine and the circulating strains, which diminishes vaccine efficacy. This necessitates new approaches that provide broader protection against influenza. Here we designed a vaccine using the hypervariable receptor-binding domain (RBD) of viral hemagglutinin displayed on a nanoparticle (np) able to elicit antibody responses that neutralize H1N1 influenza viruses spanning over 90 years. Co-display of RBDs from multiple strains across time, so that the adjacent RBDs are heterotypic, provides an avidity advantage to cross-reactive B cells. Immunization with the mosaic RBD-np elicited broader antibody responses than those induced by an admixture of nanoparticles encompassing the same set of RBDs as separate homotypic arrays. Furthermore, we identified a broadly neutralizing monoclonal antibody in a mouse immunized with mosaic RBD-np. The mosaic antigen array signifies a unique approach that subverts monotypic immunodominance and allows otherwise subdominant cross-reactive B cell responses to emerge.

PubMed: 30742080
DOI: 10.1038/s41590-018-0305-x

実験手法

X-RAY DIFFRACTION (2.01 Å)