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TitleInduction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus.
Journal, issue, pagesCell, Vol. 176, Issue 6, Page 1420-1431.e17, Year 2019
Publish dateMar 7, 2019
AuthorsJessica 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 /
PubMed AbstractRespiratory 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.
External linksCell / PubMed:30849373 / PubMed Central
MethodsEM (single particle)
Resolution6.3 Å
Structure data

EMDB-0350:
Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus
Method: EM (single particle) / Resolution: 6.3 Å

Source
  • Respiratory syncytial virus

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