title: Vaccine potential of Nipah virus-like particles.
abstract: Nipah virus (NiV) was first recognized in 1998 in a zoonotic disease outbreak associated with highly lethal febrile encephalitis in humans and a predominantly respiratory disease in pigs. Periodic deadly outbreaks, documentation of person-to-person transmission, and the potential of this virus as an agent of agroterror reinforce the need for effective means of therapy and prevention. In this report, we describe the vaccine potential of NiV virus-like particles (NiV VLPs) composed of three NiV proteins G, F and M. Co-expression of these proteins under optimized conditions resulted in quantifiable amounts of VLPs with many virus-like/vaccine desirable properties including some not previously described for VLPs of any paramyxovirus: The particles were fusogenic, inducing syncytia formation; PCR array analysis showed NiV VLP-induced activation of innate immune defense pathways; the surface structure of NiV VLPs imaged by cryoelectron microscopy was dense, ordered, and repetitive, and consistent with similarly derived structure of paramyxovirus measles virus. The VLPs were composed of all the three viral proteins as designed, and their intracellular processing also appeared similar to NiV virions. The size, morphology and surface composition of the VLPs were consistent with the parental virus, and importantly, they retained their antigenic potential. Finally, these particles, formulated without adjuvant, were able to induce neutralizing antibody response in Balb/c mice. These findings indicate vaccine potential of these particles and will be the basis for undertaking future protective efficacy studies in animal models of NiV disease.
authors.affiliation: Department of Microbiology, Center for Biodefense and Emerging Infectious Disease, University of Texas Medical Branch, Galveston, Texas, United States of America. prwalpit@utmb.edu
authors.forename: Pramila
authors.initials: P
authors.lastname: Walpita
authors.forename: Jennifer
authors.initials: J
authors.lastname: Barr
authors.forename: Michael
authors.initials: M
authors.lastname: Sherman
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Basler
authors.forename: Linfa
authors.initials: L
authors.lastname: Wang
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015726:Giant Cells / Q000821:virology; D006023:Glycoproteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D045405:Nipah Virus / Q000276:immunology* / Q000648:ultrastructure; D010957:Plasmids / Q000235:genetics; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D013045:Species Specificity; D014158:Transcription, Genetic; D014162:Transfection; D014764:Viral Proteins / Q000378:metabolism; D014765:Viral Vaccines / Q000276:immunology*; D014771:Virion / Q000276:immunology* / Q000648:ultrastructure
chemical_list: D000914:Antibodies, Viral; D006023:Glycoproteins; D014764:Viral Proteins; D014765:Viral Vaccines