TY - JOUR
T1 - Genetic engineering of live rabies vaccines
AU - Morimoto, Kinjiro
AU - McGettigan, James P.
AU - Foley, Heather D.
AU - Hooper, D. Craig
AU - Dietzschold, Bernhard
AU - Schnell, Matthias J.
N1 - Funding Information:
We thank Suchita Santosh Hodawadekar for excellent technical help. This work was supported by Public Health Service grants AI 45097 and AI 44340.
PY - 2001/5/14
Y1 - 2001/5/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0035858125&partnerID=8YFLogxK
U2 - 10.1016/S0264-410X(01)00064-0
DO - 10.1016/S0264-410X(01)00064-0
M3 - Article
C2 - 11348722
AN - SCOPUS:0035858125
SN - 0264-410X
VL - 19
SP - 3543
EP - 3551
JO - Vaccine
JF - Vaccine
IS - 25-26
ER -