Japanese encephalitis virus vaccine candidates generated by chimerization with dengue virus type 4.
Japanese encephalitis virus (JEV) is a leading cause of viral encephalitis worldwide and vaccination is one of the most effective ways to prevent disease. A suitable live-attenuated JEV vaccine could be formulated with a live-attenuated tetravalent dengue vaccine for the control of these viruses in endemic areas. Toward this goal, we generated chimeric virus vaccine candidates by replacing the precursor membrane (prM) and envelope (E) protein structural genes of recombinant dengue virus type 4 (rDEN4) or attenuated vaccine candidate rDEN4Δ30 with those of wild-type JEV strain India/78. Mutations were engineered in E, NS3 and NS4B protein genes to improve replication in Vero cells. The chimeric viruses were attenuated in mice and some elicited modest but protective levels of immunity after a single dose. One particular chimeric virus, bearing E protein mutation Q264H, replicated to higher titer in tissue culture and was significantly more immunogenic in mice. The results are compared with live-attenuated JEV vaccine strain SA14-14-2.
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States. Electronic address: gromowskig@niaid.nih.gov.
Gregory D
GD
Gromowski
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
Cai-Yen
CY
Firestone
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
Christopher T
CT
Hanson
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
Stephen S
SS
Whitehead
D000818:Animals; D001483:Base Sequence; D002522:Chlorocebus aethiops; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology*; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000276:immunology; D004672:Encephalitis, Japanese / Q000517:prevention & control*; D005260:Female; D022321:Japanese Encephalitis Vaccines / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D020365:RNA Helicases / Q000235:genetics / Q000276:immunology; D012697:Serine Endopeptidases / Q000235:genetics / Q000276:immunology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology*; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D022321:Japanese Encephalitis Vaccines; D008562:Membrane Glycoproteins; D020365:RNA Helicases; D012697:Serine Endopeptidases; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C080107:NS4B protein, flavivirus; C080628:glycoprotein E, Japanese encephalitis virus
Chimeric virus; Japanese encephalitis virus; Live-attenuated vaccine