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Rabies Vaccine

A technology of rabies virus and attenuated rabies virus, applied in the field of rabies vaccine

Inactive Publication Date: 2014-09-24
UNIV OF GEORGIA RES FOUND INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Additionally, these inactivated vaccines always include adjuvants that may cause side effects

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] Example 1 Mutated rabies virus

[0066] Mutation of N at the phosphorylation site reduces RV transcription and replication rates, leading to further attenuation

[0067] RV N plays an important role in the regulation of viral transcription and regulation, and RV N is phosphorylated on serine at position 389. Our studies demonstrated that N mutations at phosphorylation sites suppress minigenome transcription and replication rates (Yang et al., 1999, J. Virol. 73: 1661-1664). In order to determine whether the same mutation can reduce the rate of viral replication in fully infectious virus, the S389A, S389D and S389E mutations of N on the fully infectious clone L16 (Wu et al., J. Virol. 2002, 76: 4153 -4161). Mutations from S to A and S to D were found to result in a decrease in viral transcription and replication. Northern blot hybridization with the RV probe revealed an almost 90% reduction in the rate of viral transcription (mRNA) and replication (genomic RNA), espec...

Embodiment II

[0081] In the CNS, attenuated rabies virus activates, while pathogenic rabies virus evades, host innate immune responses.

[0082] Rabies virus (RV) induces encephalomyelitis in humans and animals. However, the pathogenic mechanism of rabies is not fully understood. To investigate host responses to RV infection, we used mouse genome arrays to study and compare pathological changes, especially inflammatory responses and Gene expression profiles. Oligonucleotide microarrays (Affymetrix Mouse Expression Set MOE430A) and real-time PCR were used to identify candidate genes differentially expressed in the CNS of mice infected with pathogenic SHBRV or attenuated B2C.

[0083] Extensive inflammatory responses were observed in animals infected with attenuated RV, but little or no inflammatory response was seen in mice infected with wt RV. Moreover, attenuated RV induced the expression of genes involved in innate immunity and antiviral responses, especially those related to the IFN-α...

Embodiment III

[0144] Example III. Comparison of SHBRV, B2C and L16 Rabies Viruses

[0145] Host gene expression profiling

[0146] In Example II we profiled host gene expression in a mouse model using two viruses, SHBRV and B2C. Here we describe another comparison with L16. L16 was cloned from vaccine strain SAD-B19 by reverse genetics technique (Schnell et al. Infectious RV from cloned cDNA. EMBO J. 1994;13:4195-4203; Wu et al. "Both viral transcription and replication are reduced when the rabies virus nucleoprotein is not phosphorylated (when the rabies virus nucleoprotein is not phosphorylated, viral transcription and replication are reduced)" J. Virol. 2002; 76: 4153-61). The virulence of these viruses was initially compared. Virus titers were determined in BHK cells and measured as focus forming units (ffu) and 50% intracerebral lethal dose (ICLD 50 ) and 50% of the intramuscular lethal dose (IMLD 50 ). from log ICLD 50 / ml or logIMLD 50 IC and IM pathogenicity indices were cal...

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Abstract

An attenuated rabies virus for use as a live vaccine is provided. The attenuated rabies virus expresses an immune factor that enhances immune response upon administration of the live vaccine.

Description

[0001] This application is a divisional application of the Chinese patent application 200680052741.8 "rabies vaccine" filed on December 14, 2006. [0002] This application claims the benefit of US Provisional Application No. 60 / 750,413, filed December 14, 2005, which is hereby incorporated by reference in its entirety. [0003] Statement of Government Rights [0004] This invention was made with United States Government support under Public Health Service Grant No. AI-051560 from the National Institute of Allergy and Infectious Diseases. The US Government has certain rights in this invention. Background technique [0005] Rabies virus (RV) is a highly neurotropic virus that migrates from the entry portal to the central nervous system (CNS). The virus is a non-segmented negative-sense RNA virus in the Rhabdoviridae family and induces fatal neurological diseases in humans and animals. Each year, more than 70,000 people are reported to die from the disease, and millions of ot...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N7/04A61K39/205A61P31/14
CPCC12N7/00C12N2760/20134A61K39/205C12N2760/20161A61K2039/5254A61K2039/55522C12N2760/20143A61K2039/5256A61K39/12A61P31/14
Inventor 傅振芳
Owner UNIV OF GEORGIA RES FOUND INC
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