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Characterization of rubella virus strain differences associated with attenuation
J K Chantler1, K D Lund, N P Miki
1Division of Medical Microbiology, University of British Columbia, Vancouver, Canada.
Abstract:
A comparison of the phenotypic properties of three rubella vaccines (HPV77/DE5, RA27/3 and Cendehill) and four wild-type (wt+) isolates (M33, Therien, Thomas and IB2) has been carried out. Differences in growth characteristics, plaque morphology and temperature sensitivity were identified. In addition differential reactivity of the strains to polyclonal and a monoclonal anti-E1 antibody were found in immunoperoxidase-staining reactions. The ability of the wt+ and vaccine strains to infect lymphoreticular cells and chondrocytes, also varied in that the RA27/3 and Cendehill strains were highly restricted in both these cell types while the wt+ strains and HPV77/DE5 vaccine grew to higher titer. This biological variation was associated with differences in E1 and E2 glycoproteins detected on immunoblots.
Insights
This study compared rubella vaccine strains (HPV77/DE5, RA27/3, Cendehill) with wild-type rubella virus isolates. Differences in growth, plaque morphology, and E1/E2 glycoprotein reactivity were observed, impacting infectivity in specific cell types.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Rubella virus infection poses risks, necessitating effective vaccination strategies.
- Understanding the phenotypic differences between rubella vaccine strains and wild-type isolates is crucial for vaccine efficacy and safety assessments.
Purpose of the Study:
- To compare the phenotypic properties of three rubella vaccine strains (HPV77/DE5, RA27/3, Cendehill) against four wild-type (wt+) rubella virus isolates (M33, Therien, Thomas, IB2).
- To investigate variations in growth characteristics, plaque morphology, temperature sensitivity, and reactivity to antibodies.
- To assess the differential infectivity of these strains in lymphoreticular cells and chondrocytes.
Main Methods:
- Phenotypic characterization including growth curves, plaque assays, and temperature sensitivity profiling.
- Immunoperoxidase staining using polyclonal and monoclonal anti-E1 antibodies to assess viral antigen expression.
- In vitro infection studies using lymphoreticular cells and chondrocytes.
- Immunoblot analysis to detect differences in E1 and E2 glycoproteins.
Main Results:
- Significant differences were observed in growth characteristics, plaque morphology, and temperature sensitivity among the rubella vaccine and wild-type strains.
- Differential reactivity to anti-E1 antibodies was noted, indicating variations in viral protein expression.
- Rubella vaccine strains RA27/3 and Cendehill showed restricted growth in lymphoreticular cells and chondrocytes compared to wild-type strains and HPV77/DE5.
- These biological variations correlated with detectable differences in E1 and E2 glycoproteins.
Conclusions:
- Phenotypic variations exist between different rubella vaccine strains and wild-type rubella virus isolates.
- These variations, particularly in viral glycoproteins and infectivity profiles, may influence vaccine performance and host-pathogen interactions.
- Further research into these differences can inform the development of improved rubella vaccines.