Influence of population diversity on neurovirulence potential of plaque purified L-Zagreb variants. Issue 20 (29th April 2016)

• Record Type: Journal Article
• Authors: Ivancic-Jelecki, Jelena; Forcic, Dubravko; Jagusic, Maja; Kosutic-Gulija, Tanja; Mazuran, Renata; Lang Balija, Maja; Isakov, Ofer; Shomron, Noam
• Is Part Of: Vaccine. Volume 34:Issue 20(2016)
• Page Start: 2383
• Page End: 2389
• Publication Date: 2016-04-29
• Subjects: L-Zagreb -- Mumps -- Mumps vaccine -- Virus population diversity -- Rat-based neurovirulence test -- Virus variants; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2016.03.033
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Neurovirulence basis of L-Zagreb vaccine was investigated. Six different L-Zagreb variants were isolated and characterized. No genetic markers of neurovirulence could be identified. Distinctive heterogeneity profiles were obtained for poorly neuroattenuated variants. Abstract: Background: Despite continuing research efforts, determinants of mumps virus virulence are still largely unknown. One of consequences of this is difficulty in striking a balance between efficacy and safety of live attenuated mumps vaccines. Among mumps vaccine strains associated with occurrence of postvaccinal aseptic meningitis is L-Zagreb, developed by further attenuation of vaccine strain L-3. Starting from an archived L-Zagreb sample with suboptimal neuroattenuation score, we isolated different viral variants and compared their genetic and phenotypic properties, in investigation of neurovirulence markers. Methods: Six different L-Zagreb variants were isolated by plaque purification. Their neurovirulent status was determined by rat-based neurovirulence test; population structure was determined by deep sequencing. Results: We isolated one well neuroattenuated viral variant, two marginally neuroattenuated, and three insufficiently neuroattenuated. No genetic markers of neurovirulence could be identified. None of variants had detectable amounts of defective interfering particles. Two characteristics set insufficiently neuroattenuated variants apart from less-neurovirulent ones: elevated variability level in regions 1293−3314, 5363−7773 and 9382−11657, and/or elevated number of mutations present in frequencies ≥1%. The most neurovirulent variants possessed both of these features. Conclusions: Distinctive heterogeneity profiles were obtained for insufficiently neuroattenuated L-Zagreb variants. No markers that would discriminate between marginally and well neuroattenuated variants were identified. The findings of this study may serve as a guideline during development of an improved L3/L-Zagreb vaccine strain.