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Updated: Aug 14, 2026
An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Immunogenicity and pathogenicity of temperature-sensitive modified respiratory syncytial virus in adult volunteers
Abstract:
Single temperature-sensitive (ts) mutants of a subgroup A strain of respiratory syncytial (RS) virus whose multiplication is restricted at 39 degrees C in MRC-6 cells and double ts mutants that are restricted at 38 degrees C, were obtained following mutagenesis using 5-fluorouracil and acridine-like compounds. Isolation and propagation of the parental RSS-2 strain of RS virus and its derived ts mutants were carried out entirely in MRC-5 human diploid cells. The immunogenicity and disease-producing ability of four of these mutants and the parental unmodified strain have been assessed by intranasal administration into groups of about 20 adult volunteers. The results of these trials indicate that the capacity of the parental RSS-2 strain to produce upper respiratory tract infection in adults was not diminished by limited propagation in MRC-5 cells. The mutants on the other hand were impaired in this respect to varying extents. The double mutant tslB in particular has characteristics that suggest that it may be suitable for further development as a live RS virus vaccine. It retained near normal immunogenicity and replicative ability in the upper respiratory tract, while exhibiting greatly reduced disease-producing potential.
Insights
Researchers developed temperature-sensitive (ts) respiratory syncytial (RS) virus mutants for a potential live vaccine. One double mutant, tslB, showed reduced disease potential while retaining immunogenicity, suggesting its suitability for further vaccine development.
Area of Science:
- Virology
- Vaccinology
- Microbiology
Background:
- Respiratory syncytial (RS) virus causes significant upper respiratory tract infections.
- Developing safe and effective live attenuated RS virus vaccines is a public health priority.
Purpose of the Study:
- To generate and characterize temperature-sensitive (ts) mutants of a subgroup A RS virus strain.
- To evaluate the immunogenicity and pathogenicity of these mutants in adult volunteers for potential vaccine development.
Main Methods:
- Mutagenesis of RS virus using 5-fluorouracil and acridine-like compounds to create ts mutants.
- Propagation of RS virus strains and mutants in MRC-5 human diploid cells.
- Intranasal administration of RS virus strains and mutants to adult volunteers to assess immunogenicity and disease production.
Main Results:
- The parental RSS-2 strain retained its ability to cause upper respiratory tract infections after propagation.
- RS virus mutants showed varying degrees of impairment in disease production.
- The double mutant tslB demonstrated near-normal immunogenicity and upper respiratory tract replication with significantly reduced disease potential.
Conclusions:
- Temperature-sensitive RS virus mutants were successfully generated.
- The double mutant tslB exhibits promising characteristics for a live RS virus vaccine candidate.
- Further development of tslB may lead to a safe and effective RS virus vaccine.
