Mimicking live flavivirus immunization with a noninfectious RNA vaccine.

A new genetic vaccine against flaviviruses is presented that can stimulate a comprehensive immune response similar to a live vaccine but with the safety profile of an inactivated vaccine. The principle is based on the use of noninfectious but replication-competent genomic RNA. This vaccine mimics live viral infection, although there is no spread of virus in the body. The complete replication complex is expressed, including all viral nonstructural proteins known to be targets of the humoral and cellular immune response. In addition, subviral particles consisting of the viral surface proteins prM/M and E are produced and presented to the immune system. The proof-of-principle is demonstrated with tick-borne encephalitis virus (TBEV). Because of the close genetic relationship among members of the genus Flavivirus, this principle presumably can also be applied to other pathogens of worldwide medical importance, such as dengue viruses, Japanese encephalitis virus, yellow fever virus, and West Nile vials. The vaccine consists of in vitro synthesized genomic RNA, genetically modified to abolish viral infectivity but to provide ample production and release of subviral particles. Gene-gun mediated injection of this experimental TBEV vaccine into adult mice is shown to yield a neutralizing and protective immune response.

Koffler RM, Aberle JH, Aberle SW, Allison SL, Heinz FX, Mandl CW. Mimicking live flavivirus immunization with a non-infectious RNA vaccine. Proc Natl Acad Sci U S A 2004;101:1951-6. Epub 2004 Feb 09. Available at: www.pnas.org/cgi/content/abstract/101/7/1951