Genetic engineering of live rabies vaccines.
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.
Morimoto
K
K
Department of Microbiology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, USA.
McGettigan
J P
JP
Foley
H D
HD
Hooper
D C
DC
Dietzschold
B
B
Schnell
M J
MJ
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000956:Antigens, Viral / Q000235:genetics; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005818:Genetic Engineering; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D007273:Injections, Intramuscular; D051379:Mice; D009500:Neutralization Tests; D011818:Rabies / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary; D011819:Rabies Vaccines / Q000008:administration & dosage / Q000235:genetics*; D011820:Rabies virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014774:Virulence / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D017931:DNA Primers; D006023:Glycoproteins; D011819:Rabies Vaccines; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins; C064951:glycoprotein G, Rabies virus