Characterization of M gene-deficient rabies virus with advantages of effective immunization and safety as a vaccine strain.
Matrix (M) protein of rabies virus is known to play an important role in assembly and budding of the progeny virus. We generated an M gene-deficient rabies virus, RC-HLDeltaM, using a reverse genetics system of rabies virus RC-HL strain to develop a novel type of vaccine. RC-HLDeltaM infection was confined within a single cell in mouse neuroblastoma cells. This deficient virus failed to generate the progeny virus in the cells. In contrast, RC-HLDeltaM propagated in BHK cells inductively expressing M protein. Suckling and adult mice inoculated intracerebrally with the parental RC-HL strain showed lethal infection and transient body weight loss, respectively, whereas both suckling and adult mice inoculated with RC-HLDeltaM showed no symptoms. The neutralizing antibody against rabies virus was successfully induced by intramuscular immunization with 10(5) focus-forming units of RC-HLDeltaM but not UV-inactivated RC-HL. Intranasal immunization with RC-HLDeltaM resulted in almost the same antibody titer to rabies virus as that in the case of immunization with live RC-HL strain. These findings indicate that RC-HLDeltaM is a candidate for a novel rabies vaccine that is safer and more effective than are current vaccines.
Ito
Naoto
N
Laboratory of Zoonotic Diseases, Division of Veterinary Medicine, Faculty of Applied Biological Science, Gifu University, Japan.
Sugiyama
Makoto
M
Yamada
Kentaro
K
Shimizu
Kenta
K
Takayama-Ito
Mutsuyo
M
Hosokawa
Junji
J
Minamoto
Nobuyuki
N
D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D002460:Cell Line; D045744:Cell Line, Tumor; D006224:Cricetinae; D005814:Genes, Viral; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D011819:Rabies Vaccines / Q000008:administration & dosage / Q000276:immunology*; D011820:Rabies virus / Q000235:genetics* / Q000276:immunology; D014763:Viral Matrix Proteins / Q000235:genetics*
D000914:Antibodies, Viral; D011819:Rabies Vaccines; D014763:Viral Matrix Proteins