title: Layer-By-Layer Nanoparticle Vaccines Carrying the G Protein CX3C Motif Protect against RSV Infection and Disease.
abstract: Respiratory syncytial virus (RSV) is the single most important cause of serious lower respiratory tract infections in young children; however no effective treatment or vaccine is currently available. Previous studies have shown that therapeutic treatment with a monoclonal antibody (clone 131-2G) specific to the RSV G glycoprotein CX3C motif, mediates virus clearance and decreases leukocyte trafficking to the lungs of RSV-infected mice. In this study, we show that vaccination with layer-by-layer nanoparticles (LbL-NP) carrying the G protein CX3C motif induces blocking antibodies that prevent the interaction of the RSV G protein with the fractalkine receptor (CX3CR1) and protect mice against RSV replication and disease pathogenesis. Peptides with mutations in the CX3C motif induced antibodies with diminished capacity to block G protein-CX3CR1 binding. Passive transfer of these anti-G protein antibodies to mice infected with RSV improved virus clearance and decreased immune cell trafficking to the lungs. These data suggest that vaccination with LbL-NP loaded with the CX3C motif of the RSV G protein can prevent manifestations of RSV disease by preventing the interaction between the G protein and CX3CR1 and recruitment of immune cells to the airways.
authors.affiliation: Department of Infectious Disease, College of Veterinary Medicine, University of Georgia, 111 Carlton Street, Athens, GA 30602, USA. jorquera@uga.edu.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Jorquera
authors.affiliation: Department of Infectious Disease, College of Veterinary Medicine, University of Georgia, 111 Carlton Street, Athens, GA 30602, USA. Katie.E.Oakley@gmail.com.
authors.forename: Katie E
authors.initials: KE
authors.lastname: Oakley
authors.affiliation: Artificial Cell Technologies Inc., 5 Science Park, Suite 13, New Haven, CT 06511, USA. jpowell@artificialcelltech.com.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Powell
authors.affiliation: Artificial Cell Technologies Inc., 5 Science Park, Suite 13, New Haven, CT 06511, USA. npalath@artificialcelltech.com.
authors.forename: Naveen
authors.initials: N
authors.lastname: Palath
authors.affiliation: Artificial Cell Technologies Inc., 5 Science Park, Suite 13, New Haven, CT 06511, USA. jboyd@artificialcelltech.com.
authors.forename: James G
authors.initials: JG
authors.lastname: Boyd
authors.affiliation: Department of Infectious Disease, College of Veterinary Medicine, University of Georgia, 111 Carlton Street, Athens, GA 30602, USA. ratripp@uga.edu.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Tripp
keywords: CX3C; G glycoprotein; G protein; RSV; immunity; nanoparticle; vaccine