Newcastle disease virus-like particles containing respiratory syncytial virus G protein induced protection in BALB/c mice, with no evidence of immunopathology.
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 protection from RSV. The VLP is composed of the NP and M proteins of Newcastle disease virus (NDV) and a chimeric 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 microg total VLP-H/G protein by intraperitoneal or intramuscular inoculation stimulated antibody responses to G protein which were as good as or better than those stimulated by comparable amounts of UV-inactivated RSV. Immunization of mice with two doses or even a single dose of these particles resulted in the complete protection of mice from RSV replication in the 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 previously been 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 protection against RSV.
Murawski
Matthew R
MR
Department of Molecular Genetics, University of Massachusetts Medical School, Rm. S5-250, 55 Lake Avenue North, Worcester, MA 01655, USA.
McGinnes
Lori W
LW
Finberg
Robert W
RW
Kurt-Jones
Evelyn A
EA
Massare
Michael J
MJ
Smith
Gale
G
Heaton
Penny M
PM
Fraire
Armando E
AE
Morrison
Trudy G
TG
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D002460:Cell Line; D004195:Disease Models, Animal; D015707:HN Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007114:Immunization; D008168:Lung / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009522:Newcastle disease virus / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control* / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014771:Virion / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000914:Antibodies, Viral; C502275:G glycoprotein, Respiratory syncytial virus; D015707:HN Protein; D011993:Recombinant Fusion Proteins; D022261:Respiratory Syncytial Virus Vaccines; D014760:Viral Fusion Proteins