Abstract
BackgroundRabies virus is the causative agent of rabies, a central nervous system disease that is almost invariably fatal. Currently vaccination is the most effective strategy for preventing rabies, and vaccines are most commonly produced from cultured cells. Although the vaccine strains employed in China include CTN, aG, PM and PV, there are no reports of strains that are adapted to primary chick embryo cells for use in human rabies prevention in China.ResultsRabies virus strain CTN-1 V was adapted to chick embryo cells by serial passage to obtain the CTNCEC25 strain. A virus growth curve demonstrated that the CTNCEC25 strain achieved high titers in chick embryo cells and was nonpathogenic to adult mice by intracerebral inoculation. A comparison of the structural protein genes of the CTNCEC25 strain and the CTN-1 V strain identified eight amino acid changes in the mature M, G and L proteins. The immunogenicity of the CTNCEC25 strain increased with the adaptation process in chick embryo cells and conferred high protective efficacy. The inactivated vaccine induced high antibody responses and provided full protection from an intramuscular challenge in adult mice.ConclusionsThis is the first description of a CTNCEC25 strain that was highly adapted to chick embryo cells, and both its in vitro and in vivo biological properties were characterized. Given the high immunogenicity and good propagation characteristics of the CTNCEC25 strain, it has excellent potential to be a candidate for development into a human rabies vaccine with high safety and quality characteristics for controlling rabies in China.
Highlights
Rabies virus is the causative agent of rabies, a central nervous system disease that is almost invariably fatal
We describe a highly chick embryo cells (CECs) adapted rabies virus (RABV) strain derived from a China fixed vaccine CTN-1 strain called CTNCEC25, and we investigate its biological properties in vivo and in vitro
The virus titers reached a plateau at 107.3-107.9 fluorescent focus units (FFU)/ml between passages 32 and 57, indicating that the CTN1 V strain was adapted to grow in CECs, and this virus strain was renamed the CTNCEC25 strain
Summary
Rabies virus is the causative agent of rabies, a central nervous system disease that is almost invariably fatal. Rabies reportedly causes approximately 55,000 human deaths annually throughout the world, the majority of which occur in Asia [1]. The causative agents of rabies are viruses belonging to the Lyssavirus genus in the family Rhabdoviridae of which the prototypic rabies virus (RABV) is responsible for the vast majority of cases. Between each of the five structural genes are four non-transcribed intergenic regions of different lengths. There are two non-coding regions at the end of the genome, namely the 3’ leader and the 5’ trailer, which are involved in regulating viral gene transcription and genome replication [4]
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