Production and characterization of vaccines based on flaviviruses defective in replication.
To develop new vaccine candidates for flavivirus infections, we have engineered two flaviviruses, yellow fever virus (YFV) and West Nile virus (WNV), that are deficient in replication. These defective pseudoinfectious viruses (PIVs) lack a functional copy of the capsid (C) gene in their genomes and are incapable of causing spreading infection upon infection of cells both in vivo and in vitro. However, they produce extracellular E protein in form of secreted subviral particles (SVPs) that are known to be an effective immunogen. PIVs can be efficiently propagated in trans-complementing cell lines making high levels of C or all three viral structural proteins. PIVs derived from YFV and WNV, demonstrated very high safety and immunization produced high levels of neutralizing antibodies and protective immune response. Such defective flaviviruses can be produced in large scale under low biocontainment conditions and should be useful for diagnostic or vaccine applications.
Mason
Peter W
PW
Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1019, USA.
Shustov
Alexandr V
AV
Frolov
Ilya
I
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D005260:Female; D051379:Mice; D014765:Viral Vaccines / Q000009:adverse effects / Q000096:biosynthesis* / Q000276:immunology*; D014779:Virus Replication; D014902:West Nile virus / Q000235:genetics* / Q000502:physiology*; D015005:Yellow fever virus / Q000235:genetics* / Q000502:physiology*
D014765:Viral Vaccines