Genetic engineering of live rabies vaccines

Kinjiro Morimoto, James P. McGettigan, Heather D. Foley, D. Craig Hooper, Bernhard Dietzschold, Matthias J. Schnell

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Rabies virus is not a single entity but consists of a wide array of variants that are each associated with different host species. These viruses differ greatly in the antigenic makeup of their G proteins, the primary determinant of pathogenicity and major inducer of protective immunity. Due to this diversity, existing rabies vaccines have largely been targeted to individual animal species. In this report, a novel approach to the development of rabies vaccines using genetically modified, reverse-engineered live attenuated rabies viruses is described. This approach entails the engineering of vaccine rabies virus containing G proteins from virulent strains and modification of the G protein to further reduce pathogenicity. Strategies employed included exchange of the arginine at position 333 for glutamine and modification of the cytoplasmic domain. The recombinant viruses obtained were non-neuroinvasive when administered via a peripheral route. The ability to confer protective immunity depended largely upon conservation of the G protein antigenic structure between the vaccine and challenge virus, as well as on the route of immunization.

Original languageEnglish
Pages (from-to)3543-3551
Number of pages9
JournalVaccine
Volume19
Issue number25-26
DOIs
StatePublished - 14 May 2001
Externally publishedYes

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