{"id":"doi:10.1016/j.cell.2019.01.046","kind":"article","title":"Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus","authors":["Marcandalli J","Fiala B","Ols S","Perotti M","de van der Schueren W","Snijder J","Hodge E","Benhaim M","Ravichandran R","Carter L","Sheffler W","Brunner L","Lawrenz M","Dubois P","Lanzavecchia A","Sallusto F","Lee KK","Veesler D","Correnti CE","Stewart LJ","Baker D","Loré K","Perez L","King NP"],"author_count":24,"year":2019,"published":"2019-03-01","venue":"Cell","cited_by":440,"doi":"10.1016/j.cell.2019.01.046","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.cell.2019.01.046","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.cell.2019.01.046","updated":null,"pmid":"30849373","pmcid":"PMC6424820","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC6424820/pdf","abstract":"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.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus\" by Marcandalli J, Fiala B, Ols S et al., https://doi.org/10.1016/j.cell.2019.01.046, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"infectious-disease-amr","name":"Infectious Disease, Vaccines & Antimicrobial Resistance","domain_slug":"medicine"}],"cited_in_dossiers":[]}