JVI Accepts, published online ahead of print on 4 November 2009

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J. Virol. doi:10.1128/JVI.01709-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Newcastle Disease Virus-Like Particles Containing Respiratory Syncytial Virus (RSV) G protein Induced Protection in BALB/c Mice With No Evidence of Immunopathology

Matthew R. Murawski, Lori W. McGinnes, Robert W. Finberg, Evelyn A. Kurt-Jones, Michael J. Massare, Gale Smith, Penny M. Heaton, Armando E. Fraire, and Trudy G. Morrison^*

Department of Molecular Genetics and Microbiology, Program in Immunology and Virology, Department of Medicine, Department of Pathology, University of Massachusetts Medical School, Worcester, MA; Novavax, Inc., Rockville, MD

^* To whom correspondence should be addressed. Email: trudy.morrison{at}umassmed.edu.

Respiratory syncytial virus (RSV) is the leading cause of serious respiratory infections in children as well as a serious cause of disease in elderly and immunosuppressed populations. There are no licensed vaccines available to prevent RSV disease. We have developed a virus-like particle (VLP) vaccine candidate for RSV. The VLP is composed of the NP and M proteins of Newcastle disease virus (NDV) and a chimera protein containing the cytoplasmic and transmembrane domains of the NDV HN protein and the ectodomain of the human RSV G protein (H/G). Immunization of mice with 10 or 40 μg total VLP-H/G protein by intraperitoneal or intramuscular inoculation stimulated antibody responses to G protein as good as or better than comparable amounts of UV inactivated RSV. Immunization of mice with two or even a single dose of these particles resulted in the complete protection of mice from RSV replication in murine lungs. Immunization with these particles induced neutralizing antibodies with modest titers. Upon RSV challenge of VLP-H/G immunized mice, no enhanced pathology in the lungs was observed although lungs of mice immunized in parallel with formalin inactivated RSV (FI-RSV) showed the significant pathology that has been previously documented after immunization with FI-RSV. Thus, the VLP-H/G candidate vaccine was immunogenic in BALB/c mice and prevented replication of RSV in murine lungs with no evidence of immunopathology. These data support further development of virus-like particle vaccine candidates for RSV.