TY - JOUR
T1 - Evaluations of rationally designed rift valley fever vaccine candidate RVax-1 in mosquito and rodent models
AU - Ikegami, Tetsuro
AU - Jurado-Cobena, Eduardo
AU - Alkan, Cigdem
AU - Smith, Jennifer K.
AU - Zhang, Lihong
AU - Kalveram, Birte
AU - Juelich, Terry L.
AU - Esterly, Allen T.
AU - Bhaskar, Jahnavi R.
AU - Thangamani, Saravanan
AU - Freiberg, Alexander N.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85138564421&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85138564421&partnerID=8YFLogxK
U2 - 10.1038/s41541-022-00536-3
DO - 10.1038/s41541-022-00536-3
M3 - Article
C2 - 36131104
AN - SCOPUS:85138564421
SN - 2059-0105
VL - 7
JO - npj Vaccines
JF - npj Vaccines
IS - 1
M1 - 109
ER -