Genetic stability of Rift Valley fever virus MP-12 vaccine during serial passages in culture cells

Nandadeva Lokugamage, Tetsuro Ikegami

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Rift Valley fever is a mosquito-borne zoonotic disease endemic to Africa, which affects both ruminants and humans. Rift Valley fever causes serious damage to the livestock industry and is also a threat to public health. The Rift Valley fever virus has a segmented negative-stranded RNA genome consisting of Large (L)-segment, Medium (M)-segment, and Small (S)-segment. The live-attenuated MP-12 vaccine is immunogenic in livestock and humans, and is conditionally licensed for veterinary use in the US. The MP-12 strain encodes 23 mutations (nine amino acid substitutions) and is attenuated through a combination of mutations in the L-segment, M-segment, and S-segment. Among them, the M-U795C, M-A3564G, and L-G3104A mutations contribute to viral attenuation through the L-segment and M-segment. The M-U795C, M-A3564G, L-U533C, and L-G3750A mutations are also independently responsible for temperature-sensitive phenotype. We hypothesized that a serial passage of the MP-12 vaccine in culture cells causes reversions of the MP-12 genome. The MP-12 vaccine and recombinant rMP12-ΔNSs16/198 were serially passaged 25 times. Droplet digital polymerase chain reaction analysis revealed that the reversion occurred at L-G3750A during passages of MP-12 in Vero or MRC-5 cells. The reversion also occurred at M-A3564G and L-U533C of rMP12-ΔNSs16/198 in Vero cells. Reversion mutations were not found in MP-12 or the variant, rMP12-TOSNSs, in the brains of mice with encephalitis. This study characterized genetic stability of the MP-12 vaccine and the potential risk of reversion mutation at the L-G3750A temperature-sensitive mutation after excessive viral passages in culture cells.

Original languageEnglish (US)
Article number20
Journalnpj Vaccines
Volume2
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

Rift Valley fever virus
Serial Passage
Vaccines
Cell Culture Techniques
Mutation
Rift Valley Fever
Livestock
Genome
Synthetic Vaccines
Temperature
Vero Cells
Zoonoses
Ruminants
Encephalitis
Amino Acid Substitution
Culicidae
Industry
Public Health
RNA
Phenotype

ASJC Scopus subject areas

  • Pharmacology
  • Infectious Diseases
  • Immunology
  • Pharmacology (medical)

Cite this

Genetic stability of Rift Valley fever virus MP-12 vaccine during serial passages in culture cells. / Lokugamage, Nandadeva; Ikegami, Tetsuro.

In: npj Vaccines, Vol. 2, No. 1, 20, 01.12.2017.

Research output: Contribution to journalArticle

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