npj Vaccines (Sep 2022)

Evaluations of rationally designed rift valley fever vaccine candidate RVax-1 in mosquito and rodent models

  • Tetsuro Ikegami,
  • Eduardo Jurado-Cobena,
  • Cigdem Alkan,
  • Jennifer K. Smith,
  • Lihong Zhang,
  • Birte Kalveram,
  • Terry L. Juelich,
  • Allen T. Esterly,
  • Jahnavi R. Bhaskar,
  • Saravanan Thangamani,
  • Alexander N. Freiberg

DOI
https://doi.org/10.1038/s41541-022-00536-3
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 12

Abstract

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Abstract Rift Valley fever (RVF) is a mosquito-borne zoonosis endemic to Africa and the Arabian Peninsula, which causes large outbreaks among humans and ruminants. Single dose vaccinations using live-attenuated RVF virus (RVFV) support effective prevention of viral spread in endemic countries. Due to the segmented nature of RVFV genomic RNA, segments of vaccine strain-derived genomic RNA could be incorporated into wild-type RVFV within co-infected mosquitoes or animals. Rationally designed vaccine candidate RVax-1 displays protective epitopes fully identical to the previously characterized MP-12 vaccine. Additionally, all genome segments of RVax-1 contribute to the attenuation phenotype, which prevents the formation of pathogenic reassortant strains. This study demonstrated that RVax-1 cannot replicate efficiently in orally fed Aedes aegypti mosquitoes, while retaining strong immunogenicity and protective efficacy in an inbred mouse model, which were indistinguishable from the MP-12 vaccine. These findings support further development of RVax-1 as the next generation MP-12-based vaccine for prevention of Rift Valley fever in humans and animals.