4.6 Article

RSV N-nanorings fused to palivizumab-targeted neutralizing epitope as a nanoparticle RSV vaccine

Journal

NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 13, Issue 2, Pages 411-420

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2016.08.006

Keywords

Respiratory syncytial virus; Epitope-focused vaccine; Nucleoprotein nanoparticles; Mucosal vaccine; F glycoprotein

Funding

  1. Agence Nationale de la Recherche [ANR-12-RPIB-0004-02]

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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 byRSV nucleoprotein (N) as an RSVvaccine, 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. (C) 2016 Elsevier Inc. All rights reserved.

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