Attenuation and protective efficacy of Rift Valley fever phlebovirus rMP12-GM50 strain

Hoai J. Ly, Shoko Nishiyama, Nandadeva Lokugamage, Jennifer K. Smith, Lihong Zhang, David Perez, Terry L. Juelich, Alexander Freiberg, Tetsuro Ikegami

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and the Arabian Peninsula that affects sheep, cattle, goats, camels, and humans. Effective vaccination of susceptible ruminants is important for the prevention of RVF outbreaks. Live-attenuated RVF vaccines are in general highly immunogenic in ruminants, whereas residual virulence might be a concern for vulnerable populations. It is also important for live-attenuated strains to encode unique genetic markers for the differentiation from wild-type RVFV strains. In this study, we aimed to strengthen the attenuation profile of the MP-12 vaccine strain via the introduction of 584 silent mutations. To minimize the impact on protective efficacy, codon usage and codon pair bias were not de-optimized. The resulting rMP12-GM50 strain showed 100% protective efficacy with a single intramuscular dose, raising a 1:853 mean titer of plaque reduction neutralization test. Moreover, outbred mice infected with one of three pathogenic reassortant ZH501 strains, which encoded rMP12-GM50 L-, M-, or S-segments, showed 90%, 50%, or 30% survival, respectively. These results indicate that attenuation of the rMP12-GM50 strain is significantly attenuated via the L-, M-, and S-segments. Recombinant RVFV vaccine strains encoding similar silent mutations will be also useful for the surveillance of reassortant strains derived from vaccine strains in endemic countries.

Original languageEnglish (US)
JournalVaccine
DOIs
StateAccepted/In press - 2017

Fingerprint

Phlebovirus
Rift Valley Fever
Rift Valley fever
Vaccines
Ruminants
Codon
Camelus
Neutralization Tests
Synthetic Vaccines
Zoonoses
Vulnerable Populations
Culicidae
Genetic Markers
Goats
Disease Outbreaks
Virulence
Sheep
Vaccination
vaccines
codons

Keywords

  • Attenuation
  • MP-12 vaccine
  • Protective efficacy
  • Reverse genetics
  • Rift Valley fever phlebovirus
  • Silent mutation

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

Cite this

Attenuation and protective efficacy of Rift Valley fever phlebovirus rMP12-GM50 strain. / Ly, Hoai J.; Nishiyama, Shoko; Lokugamage, Nandadeva; Smith, Jennifer K.; Zhang, Lihong; Perez, David; Juelich, Terry L.; Freiberg, Alexander; Ikegami, Tetsuro.

In: Vaccine, 2017.

Research output: Contribution to journalArticle

Ly, Hoai J. ; Nishiyama, Shoko ; Lokugamage, Nandadeva ; Smith, Jennifer K. ; Zhang, Lihong ; Perez, David ; Juelich, Terry L. ; Freiberg, Alexander ; Ikegami, Tetsuro. / Attenuation and protective efficacy of Rift Valley fever phlebovirus rMP12-GM50 strain. In: Vaccine. 2017.
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abstract = "Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and the Arabian Peninsula that affects sheep, cattle, goats, camels, and humans. Effective vaccination of susceptible ruminants is important for the prevention of RVF outbreaks. Live-attenuated RVF vaccines are in general highly immunogenic in ruminants, whereas residual virulence might be a concern for vulnerable populations. It is also important for live-attenuated strains to encode unique genetic markers for the differentiation from wild-type RVFV strains. In this study, we aimed to strengthen the attenuation profile of the MP-12 vaccine strain via the introduction of 584 silent mutations. To minimize the impact on protective efficacy, codon usage and codon pair bias were not de-optimized. The resulting rMP12-GM50 strain showed 100{\%} protective efficacy with a single intramuscular dose, raising a 1:853 mean titer of plaque reduction neutralization test. Moreover, outbred mice infected with one of three pathogenic reassortant ZH501 strains, which encoded rMP12-GM50 L-, M-, or S-segments, showed 90{\%}, 50{\%}, or 30{\%} survival, respectively. These results indicate that attenuation of the rMP12-GM50 strain is significantly attenuated via the L-, M-, and S-segments. Recombinant RVFV vaccine strains encoding similar silent mutations will be also useful for the surveillance of reassortant strains derived from vaccine strains in endemic countries.",
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