title: RSV N-nanorings fused to palivizumab-targeted neutralizing epitope as a nanoparticle RSV vaccine.
abstract: Respiratory syncytial virus (RSV) is the leading cause of acute respiratory infections in children, yet no vaccine is available. The sole licensed preventive treatment against RSV is composed of a monoclonal neutralizing antibody (palivizumab), which targets a conformational epitope located on the fusion protein (F). Palivizumab reduces the burden of bronchiolitis but does not prevent infection. Thus, the development of RSV vaccines remains a priority. We previously evaluated nanorings formed by RSV nucleoprotein (N) as an RSV vaccine, as well as an immunostimulatory carrier for heterologous antigens. Here, we linked the palivizumab-targeted epitope (called FsII) to N, to generate N-FsII-nanorings. Intranasal N-FsII immunization elicited anti-F antibodies in mice that were non-neutralizing in vitro. Nevertheless, RSV-challenged animals were better protected against virus replication than mice immunized with N-nanorings, especially in the upper airways. In conclusion, an N-FsII-focused vaccine is an attractive candidate combining N-specific cellular immunity and F-specific antibodies for protection.
authors.affiliation: VIM, INRA, Université Paris-Saclay, Jouy-en-Josas, France. Electronic address: pierre-louis.herve@dbv-technologies.com.
authors.forename: Pierre-Louis
authors.initials: PL
authors.lastname: Hervé
authors.affiliation: VIM, INRA, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Deloizy
authors.affiliation: VIM, INRA, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Delphyne
authors.initials: D
authors.lastname: Descamps
authors.affiliation: INSERM U1173, UFR Simone Veil, UVSQ, Saint-Quentin en Yvelines, France; AP-HP, Ambroise Paré Hospital, Microbiology Laboratory, Boulogne-Billancourt, France.
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Rameix-Welti
authors.affiliation: VIM, INRA, Université Paris-Saclay, Jouy-en-Josas, France.
authors.forename: Jenna
authors.initials: J
authors.lastname: Fix
authors.affiliation: Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors.forename: Jason S
authors.initials: JS
authors.lastname: McLellan
authors.affiliation: VIM, INRA, Université Paris-Saclay, Jouy-en-Josas, France. Electronic address: jean-francois.eleouet@jouy.inra.fr.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Eléouët
authors.affiliation: VIM, INRA, Université Paris-Saclay, Jouy-en-Josas, France. Electronic address: sabine.riffault@jouy.inra.fr.
authors.forename: Sabine
authors.initials: S
authors.lastname: Riffault
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D006801:Humans; D051379:Mice; D053758:Nanoparticles; D000069455:Palivizumab; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control; D022261:Respiratory Syncytial Virus Vaccines; D012136:Respiratory Syncytial Viruses; D016205:Sigmodontinae; D014760:Viral Fusion Proteins
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D022261:Respiratory Syncytial Virus Vaccines; D014760:Viral Fusion Proteins; D000069455:Palivizumab
keywords: Epitope-focused vaccine; F glycoprotein; Mucosal vaccine; Nucleoprotein nanoparticles; Respiratory syncytial virus