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Generation of a Single-Cycle Replicable Rift Valley Fever Vaccine

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Vaccine Design

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1403))

Abstract

Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) is an arbovirus that causes severe disease in humans and livestock in sub-Saharan African countries. The virus carries a tripartite, single-stranded, and negative–sense RNA genome, designated as L, M, and S RNAs. RVFV spread can be prevented by the effective vaccination of animals and humans. Although the MP-12 strain of RVFV is a live attenuated vaccine candidate, MP-12 showed neuroinvasiveness and neurovirulence in young mice and immunodeficiency mice. Hence, there is a concern for the use of MP-12 to certain individuals, especially those that are immunocompromised. To improve MP-12 safety, we have generated a single-cycle, replicable MP-12 (scMP-12), which carries L RNA, S RNA encoding green fluorescent protein in place of a viral nonstructural protein NSs, and an M RNA encoding a mutant envelope protein lacking an endoplasmic reticulum retrieval signal and defective for membrane fusion function. The scMP-12 undergoes efficient amplification in the Vero-G cell line, which is a Vero cell line stably expressing viral envelope proteins, while it undergoes single-cycle replication in naïve cells and completely lacks neurovirulence in suckling mice after intracranial inoculation. A single-dose vaccination of mice with scMP-12 confers protective immunity. Thus, scMP-12 represents a new, promising RVF vaccine candidate. Here we describe protocols for scMP-12 generation by using a reverse genetics system, establishment of Vero-G cells, and titration of scMP-12 in Vero-G cells.

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References

  1. Bird BH, Nichol ST (2012) Breaking the chain: Rift Valley fever virus control via livestock vaccination. Curr Opin Virol 2:315–323

    Article  CAS  PubMed  Google Scholar 

  2. Caplen H, Peters CJ, Bishop DH (1985) Mutagen-directed attenuation of Rift Valley fever virus as a method for vaccine development. J Gen Virol 66(Pt 10):2271–2277

    Article  PubMed  Google Scholar 

  3. Morrill JC, Jennings GB, Caplen H, Turell MJ, Johnson AJ, Peters CJ (1987) Pathogenicity and immunogenicity of a mutagen-attenuated Rift Valley fever virus immunogen in pregnant ewes. Am J Vet Res 48:1042–1047

    CAS  PubMed  Google Scholar 

  4. Balkhy HH, Memish ZA (2003) Rift Valley fever: an uninvited zoonosis in the Arabian peninsula. Int J Antimicrob Agents 21:153–157

    Article  CAS  PubMed  Google Scholar 

  5. Peters CJ, Meegan JM (1989) Rift Valley fever virus. CRC Press, Boca Raton, FL

    Google Scholar 

  6. Peters CJ, LeDuc JW (1999) Bunyaviruses, phleboviruses, and related viruses. In: Belshe RB (ed) Textbook of human Virology. Mosby Year Book, St.Louis, pp 571–614

    Google Scholar 

  7. Gargan TP, Clark GG, Dohm DJ, Turell MJ, Bailey CL (1988) Vector potential of selected North American mosquito species for Rift Valley fever virus. Am J Trop Med Hyg 38:440–446

    PubMed  Google Scholar 

  8. Sidwell RW, Smee DF (2003) Viruses of the Bunya- and Togaviridae families: potential as bioterrorism agents and means of control. Antiviral Res 57:101–111

    Article  CAS  PubMed  Google Scholar 

  9. Ikegami T, Makino S (2009) Rift valley fever vaccines. Vaccine 27(Suppl 4):D69–D72

    Article  CAS  PubMed  Google Scholar 

  10. Besselaar TG, Blackburn NK, Meenehan GM (1991) Antigenic analysis of Rift Valley fever virus isolates: monoclonal antibodies distinguish between wild-type and neurotropic virus strains. Res Virol 142:469–474

    Article  CAS  PubMed  Google Scholar 

  11. Shope RE, Peters CJ, Walker JS (1980) Serological relation between Rift Valley fever virus and viruses of phlebotomus fever serogroup. Lancet 1:886–887

    Article  CAS  PubMed  Google Scholar 

  12. Tesh RB, Peters CJ, Meegan JM (1982) Studies on the antigenic relationship among phleboviruses. Am J Trop Med Hyg 31:149–155

    CAS  PubMed  Google Scholar 

  13. Anderson GW, Smith JF (1987) Immunoelectron microscopy of Rift Valley fever viral morphogenesis in primary rat hepatocytes. Virology 161:91–100

    Article  PubMed  Google Scholar 

  14. Besselaar TG, Blackburn NK (1991) Topological mapping of antigenic sites on the Rift Valley fever virus envelope glycoproteins using monoclonal antibodies. Arch Virol 121:111–124

    Article  CAS  PubMed  Google Scholar 

  15. Harrington DG, Lupton HW, Crabbs CL, Peters CJ, Reynolds JA, Slone TW Jr (1980) Evaluation of a formalin-inactivated Rift Valley fever vaccine in sheep. Am J Vet Res 41:1559–1564

    CAS  PubMed  Google Scholar 

  16. Niklasson BS, Meadors GF, Peters CJ (1984) Active and passive immunization against Rift Valley fever virus infection in Syrian hamsters. Acta Pathol Microbiol Immunol Scand C 92:197–200

    CAS  PubMed  Google Scholar 

  17. Peters CJ, Reynolds JA, Slone TW, Jones DE, Stephen EL (1986) Prophylaxis of Rift Valley fever with antiviral drugs, immune serum, an interferon inducer, and a macrophage activator. Antiviral Res 6:285–297

    Article  CAS  PubMed  Google Scholar 

  18. Peters CJ, Jones D, Trotter R, Donaldson J, White J, Stephen E, Slone TW Jr (1988) Experimental Rift Valley fever in rhesus macaques. Arch Virol 99:31–44

    Article  CAS  PubMed  Google Scholar 

  19. Pittman PR, Liu CT, Cannon TL, Makuch RS, Mangiafico JA, Gibbs PH, Peters CJ (1999) Immunogenicity of an inactivated Rift Valley fever vaccine in humans: a 12-year experience. Vaccine 18:181–189

    Article  CAS  PubMed  Google Scholar 

  20. Schmaljohn CS, Parker MD, Ennis WH, Dalrymple JM, Collett MS, Suzich JA, Schmaljohn AL (1989) Baculovirus expression of the M genome segment of Rift Valley fever virus and examination of antigenic and immunogenic properties of the expressed proteins. Virology 170:184–192

    Article  CAS  PubMed  Google Scholar 

  21. Spik K, Shurtleff A, McElroy AK, Guttieri MC, Hooper JW, SchmalJohn C (2006) Immunogenicity of combination DNA vaccines for Rift Valley fever virus, tick-borne encephalitis virus, Hantaan virus, and Crimean Congo hemorrhagic fever virus. Vaccine 24:4657–4666

    Article  CAS  PubMed  Google Scholar 

  22. Baskerville A, Hubbard KA, Stephenson JR (1992) Comparison of the pathogenicity for pregnant sheep of Rift Valley fever virus and a live attenuated vaccine. Res Vet Sci 52:307–311

    Article  CAS  PubMed  Google Scholar 

  23. Hubbard KA, Baskerville A, Stephenson JR (1991) Ability of a mutagenized virus variant to protect young lambs from Rift Valley fever. Am J Vet Res 52:50–55

    CAS  PubMed  Google Scholar 

  24. Morrill JC, Carpenter L, Taylor D, Ramsburg HH, Quance J, Peters CJ (1991) Further evaluation of a mutagen-attenuated Rift Valley fever vaccine in sheep. Vaccine 9:35–41

    Article  CAS  PubMed  Google Scholar 

  25. Morrill JC, Mebus CA, Peters CJ (1997) Safety of a mutagen-attenuated Rift Valley fever virus vaccine in fetal and neonatal bovids. Am J Vet Res 58:1110–1114

    CAS  PubMed  Google Scholar 

  26. Morrill JC, Mebus CA, Peters CJ (1997) Safety and efficacy of a mutagen-attenuated Rift Valley fever virus vaccine in cattle. Am J Vet Res 58:1104–1109

    CAS  PubMed  Google Scholar 

  27. Morrill JC, Peters CJ (2003) Pathogenicity and neurovirulence of a mutagen-attenuated Rift Valley fever vaccine in rhesus monkeys. Vaccine 21:2994–3002

    Article  CAS  PubMed  Google Scholar 

  28. Murakami S, Terasaki K, Ramirez SI, Morrill JC, Makino S (2014) Development of a novel, single-cycle replicable rift valley fever vaccine. PLoS Negl Trop Dis 8:e2746

    Article  PubMed  PubMed Central  Google Scholar 

  29. Ikegami T, Won S, Peters CJ, Makino S (2006) Rescue of infectious rift valley fever virus entirely from cDNA, analysis of virus lacking the NSs gene, and expression of a foreign gene. J Virol 80:2933–2940

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Buchholz UJ, Finke S, Conzelmann KK (1999) Generation of bovine respiratory syncytial virus (BRSV) from cDNA: BRSV NS2 is not essential for virus replication in tissue culture, and the human RSV leader region acts as a functional BRSV genome promoter. J Virol 73:251–259

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Keegan K, Collett MS (1986) Use of bacterial expression cloning to define the amino acid sequences of antigenic determinants on the G2 glycoprotein of Rift Valley fever virus. J Virol 58:263–270

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Robert Tesh, C. J. Peters, and Tetsuro Ikegami for anti-MP-12 antibody, monoclonal antibodies against Gn, and bacterially expressed N protein used for anti-N protein antibody production, respectively. This work was supported by Public Health Service grant AI101772, and in part by the John Sealy Memorial Endowment Fund for Biomedical Research. S. Murakami was supported by the James W. McLaughlin Fellowship fund and by a research fellowship from the Japan Society for the Promotion of Science.

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Correspondence to Shin Murakami .

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Murakami, S., Terasaki, K., Makino, S. (2016). Generation of a Single-Cycle Replicable Rift Valley Fever Vaccine. In: Thomas, S. (eds) Vaccine Design. Methods in Molecular Biology, vol 1403. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3387-7_9

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  • DOI: https://doi.org/10.1007/978-1-4939-3387-7_9

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3385-3

  • Online ISBN: 978-1-4939-3387-7

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