A respiratory syncytial virus (RSV) F protein nanoparticle vaccine focuses antibody responses to a conserved neutralization domain
Open Access
- 19 May 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Immunology
- Vol. 5 (47)
- https://doi.org/10.1126/sciimmunol.aba6466
Abstract
A stabilized form of the respiratory syncytial virus (RSV) fusion (F) protein has been explored as a vaccine to prevent viral infection because it presents several potent neutralizing epitopes. Here, we used a structure-based rational design to optimize antigen presentation and focus antibody (Ab) responses to key epitopes on the pre-fusion (pre-F) protein. This protein was fused to ferritin nanoparticles (pre-F-NP) and modified with glycans to mask nonneutralizing or poorly neutralizing epitopes to further focus the Ab response. The multimeric pre-F-NP elicited durable pre-F–specific Abs in nonhuman primates (NHPs) after >150 days and elicited potent neutralizing Ab (NAb) responses in mice and NHPs in vivo, as well as in human cells evaluated in the in vitro MIMIC system. This optimized pre-F-NP stimulated a more potent Ab response than a representative pre-F trimer, DS-Cav1. Collectively, this pre-F vaccine increased the generation of NAbs targeting the desired pre-F conformation, an attribute that facilitates the development of an effective RSV vaccine.Keywords
Funding Information
- Sanofi Genzyme
This publication has 59 references indexed in Scilit:
- Structure of Respiratory Syncytial Virus Fusion Glycoprotein in the Postfusion Conformation Reveals Preservation of Neutralizing EpitopesJournal of Virology, 2011
- Structural basis for immunization with postfusion respiratory syncytial virus fusion F glycoprotein (RSV F) to elicit high neutralizing antibody titersProceedings of the National Academy of Sciences of the United States of America, 2011
- Coupling sensitive in vitro and in silico techniques to assess cross-reactive CD4+ T cells against the swine-origin H1N1 influenza virusVaccine, 2011
- Ferritin in the field of nanodevicesBiochimica et Biophysica Acta (BBA) - General Subjects, 2010
- A Toolbox for ab initio 3-D reconstructions in single-particle electron microscopyJournal of Structural Biology, 2010
- Structural basis of respiratory syncytial virus neutralization by motavizumabNature Structural & Molecular Biology, 2010
- DoG Picker and TiltPicker: Software tools to facilitate particle selection in single particle electron microscopyJournal of Structural Biology, 2009
- Humoral immunity to respiratory syncytial virus in young and elderly adultsEpidemiology and Infection, 2009
- Automated molecular microscopy: The new Leginon systemJournal of Structural Biology, 2005
- XMIPP: a new generation of an open-source image processing package for electron microscopyJournal of Structural Biology, 2004