ジャーナル: Cell / 年: 2019 タイトル: Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus. 著者: Jessica Marcandalli / Brooke Fiala / Sebastian Ols / Michela Perotti / Willem de van der Schueren / Joost Snijder / Edgar Hodge / Mark Benhaim / Rashmi Ravichandran / Lauren Carter / Will ...著者: Jessica Marcandalli / Brooke Fiala / Sebastian Ols / Michela Perotti / Willem de van der Schueren / Joost Snijder / Edgar Hodge / Mark Benhaim / Rashmi Ravichandran / Lauren Carter / Will Sheffler / Livia Brunner / Maria Lawrenz / Patrice Dubois / Antonio Lanzavecchia / Federica Sallusto / Kelly K Lee / David Veesler / Colin E Correnti / Lance J Stewart / David Baker / Karin Loré / Laurent Perez / Neil P King / 要旨: Respiratory syncytial virus (RSV) is a worldwide public health concern for which no vaccine is available. Elucidation of the prefusion structure of the RSV F glycoprotein and its identification as ...Respiratory syncytial virus (RSV) is a worldwide public health concern for which no vaccine is available. Elucidation of the prefusion structure of the RSV F glycoprotein and its identification as the main target of neutralizing antibodies have provided new opportunities for development of an effective vaccine. Here, we describe the structure-based design of a self-assembling protein nanoparticle presenting a prefusion-stabilized variant of the F glycoprotein trimer (DS-Cav1) in a repetitive array on the nanoparticle exterior. The two-component nature of the nanoparticle scaffold enabled the production of highly ordered, monodisperse immunogens that display DS-Cav1 at controllable density. In mice and nonhuman primates, the full-valency nanoparticle immunogen displaying 20 DS-Cav1 trimers induced neutralizing antibody responses ∼10-fold higher than trimeric DS-Cav1. These results motivate continued development of this promising nanoparticle RSV vaccine candidate and establish computationally designed two-component nanoparticles as a robust and customizable platform for structure-based vaccine design.
分子 #1: Engineered respiratory syncytial virus F protein (DS-Cav-1) fused...
分子
名称: Engineered respiratory syncytial virus F protein (DS-Cav-1) fused to the foldon and to the trimeric component of I53-50 (DS-Cav1-I53-50A) タイプ: protein_or_peptide / ID: 1 / 光学異性体: LEVO