Murray Valley encephalitis virus recombinant subviral particles protect mice from lethal challenge with virulent wild-type virus.
We report on the development and characterisation of a recombinant Murray Valley encephalitis virus (MVE) envelope glycoprotein expression system that results in the secretion of subviral particles (SVPs) upon transfection of the murine fibroblast (COS-7) cell line. Initially, aspects of the physical and antigenic structure of cell-associated and secreted forms of the MVE envelope glycoproteins (prM and E) are presented. We then show that BALB/c mice inoculated with SVPs purified from pcDNA(3)-prM/E-transfected COS-7 cell supernatants are protected from lethal challenge with the virulent prototype strain MVE-1-51 and that this protection correlates with the development of a neutralising humoral immune response by the host. By contrast, prior immunisation with cell-associated, recombinant MVE envelope glycoproteins did not protect mice from challenge with MVE-1-51 and this was associated with the development of antibody that was unable to neutralise virus infectivity in vitro. These studies demonstrate that SVPs derived from the in vitro expression of recombinant MVE prM and E genes are an effective candidate vaccine for the prevention of encephalitis in the mouse model.
Department of Microbiology, The University of Western Australia, Queen Elizabeth II Medical Centre, Nedlands, Australia.
M A
MA
Kroeger
P C
PC
McMinn
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D018068:Encephalitis Virus, Murray Valley / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D004671:Encephalitis, Arbovirus / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D011995:Recombination, Genetic; D014162:Transfection; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014765:Viral Vaccines / Q000276:immunology*; D014771:Virion / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D014774:Virulence
D000914:Antibodies, Viral; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C072281:E protein TH Sman, Dengue virus