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Sequence diversity of Jeryl Lynn strain of mumps virus: quantitative mutant analysis for vaccine quality control
Georgios Amexis1, Steven Rubin, Vladimir Chizhikov
1Center for Biologics Evaluation and Research, FDA Rockville, Maryland 20852, USA.
Abstract:
The Jeryl Lynn strain of mumps vaccine live (MVL) was developed in 1966 by Merck Co. and has been widely used in the U.S. and other countries since the early 1970s. Partial sequencing has recently shown that the vaccine contains a mixture of two substrains with substantially different nucleotide sequences. We have determined the complete genomic sequences of both substrains and identified 414 nucleotide differences (2.69%), leading to 87 amino acid substitutions (1.67%). We used this information to develop methods for quantification of the substrain components in vaccine samples based on PCR and restriction enzyme cleavage and oligonucleotide microarray hybridization and monitored their dynamics in viral populations propagated in different conditions. Passaging Jeryl Lynn strain in Vero or CEF cell cultures resulted in rapid selection of the major component JL1, while growth in embryonated chicken eggs (ECE) favored accumulation of the minor component JL2. Based on the findings presented here, it is proposed that the substrain composition of Jeryl Lynn vaccine can be monitored as a part of its quality control to ensure consistency of the vaccine.
Insights
The Jeryl Lynn mumps vaccine live (MVL) contains two substrains. Vaccine production conditions influence the selection of these substrains, suggesting composition monitoring for quality control.
Area of Science:
- Virology
- Vaccinology
- Molecular Biology
Background:
- The Jeryl Lynn strain of mumps vaccine live (MVL) has been a widely used vaccine since the 1970s.
- Recent partial sequencing revealed MVL contains a mixture of two distinct substrains.
- Understanding substrain composition is crucial for vaccine consistency.
Purpose of the Study:
- To fully characterize the genomic sequences of the two MVL substrains.
- To develop methods for quantifying substrain components in vaccine samples.
- To investigate the dynamics of substrain selection under different propagation conditions.
Main Methods:
- Complete genome sequencing of both MVL substrains.
- Development of PCR and microarray-based quantification methods.
- Monitoring substrain dynamics in cell cultures (Vero, CEF) and embryonated chicken eggs (ECE).
Main Results:
- Identified 414 nucleotide differences and 87 amino acid substitutions between the two substrains.
- Passaging in Vero or CEF cells selected for the major substrain (JL1).
- Growth in ECE favored the accumulation of the minor substrain (JL2).
Conclusions:
- The substrain composition of the Jeryl Lynn vaccine is influenced by propagation methods.
- Monitoring substrain composition can be a valuable part of MVL quality control.
- Ensuring consistent substrain composition is key to vaccine efficacy and safety.