Construction and evaluation of a chimeric pseudoinfectious virus vaccine to prevent Japanese encephalitis.
Multiple vaccines exist to control Japanese encephalitis (JE), but all suffer from problems. We have developed a new type of flavivirus vaccine, a pseudoinfectious virus (RepliVAX WN) that prevents West Nile virus (WNV)-induced disease. Here, we describe production of a chimeric RepliVAX (RepliVAX JE) that expresses the JE virus (JEV) prM and E proteins. Our prototype RepliVAX JE replicated poorly in cells, but blind passage produced a better-growing derivative, and analyses of this derivative allowed us to engineer a second-generation RepliVAX (RepliVAX JE.2) that grew to high titers. RepliVAX JE.2 elicited neutralizing antibodies in both mice and hamsters and provided 100% protection from a lethal challenge with JEV or WNV, respectively. These results demonstrate the utility our RepliVAX platform for producing a JE vaccine.
Ishikawa
Tomohiro
T
Department of Pathology, University of Texas Medical Branch (UTMB), 301 University Boulevard, Galveston, TX 77555-0436, United States.
Widman
Douglas G
DG
Bourne
Nigel
N
Konishi
Eiji
E
Mason
Peter W
PW
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D006224:Cricetinae; D004672:Encephalitis, Japanese / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D022321:Japanese Encephalitis Vaccines / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D009500:Neutralization Tests; D016019:Survival Analysis; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology; D014901:West Nile Fever / Q000517:prevention & control; D014902:West Nile virus / Q000235:genetics / Q000254:growth & development
D000914:Antibodies, Viral; D022321:Japanese Encephalitis Vaccines; D014614:Vaccines, Synthetic; D014764:Viral Proteins