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Published on: May 2, 2019
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Study on an attenuated rabies virus strain CTN181-3.
Leitai Shi1, Jian Zou2, Yuhua Li1
1National Institutes for Food and Drug Control, Beijing, 102629, China.
Summary
A novel attenuated rabies virus, CTN181-3, demonstrates safety and high immunogenicity in animal models. This strain shows promise as a candidate for a new oral rabies vaccine.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Rabies remains a significant public health concern globally.
- Development of effective and safe rabies vaccines is crucial for disease control.
- Attenuated virus strains are essential for vaccine development.
Purpose of the Study:
- To comprehensively characterize the attenuated rabies virus strain CTN181-3.
- To evaluate the safety, immunogenicity, and stability of CTN181-3.
- To assess its potential as an oral rabies vaccine candidate.
Main Methods:
- Pathogenicity studies in mice and golden hamsters via intracerebral (i.c.) and oral (o.i.) inoculation.
- Immunogenicity assessment through intramuscular (i.m.) and oral (o.i.) vaccination in mice and hamsters, measuring neutralizing antibodies and seroconversion.
- Cellular immune response evaluation.
- Post-exposure prophylaxis (PEP) efficacy studies in golden hamsters.
- Molecular analysis of attenuation basis.
- Stability assessment through multiple passages in vivo and in vitro.
- Gene homology comparison with Chinese rabies isolates.
Main Results:
- CTN181-3 exhibited no pathogenicity in adult mice and hamsters, with reduced pathogenicity in younger mice.
- High immunogenicity was observed, inducing high neutralizing antibody titers (>5.0 IU/ml GMT) and 100% seroconversion after a single dose.
- Significant protection was achieved in post-exposure prophylaxis models.
- Molecular analysis identified key substitutions responsible for attenuation.
- The strain demonstrated high phenotypic and genotypic stability with no reversion observed.
- CTN181-3 showed greater gene homology to Chinese rabies isolates compared to existing vaccine strains.
Conclusions:
- CTN181-3 is a safe and highly immunogenic attenuated rabies virus strain.
- Its stability and genetic characteristics make it a promising candidate for an oral rabies vaccine.
- Further development of CTN181-3 could contribute to improved rabies control strategies.
