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 - Funding Information:
The authors thank Drs. A.B. Barrett, T.L. Brasel, and D.W.C. Beasley at The University of Texas Medical Branch at Galveston (UTMB) for their helpful discussion on RVF candidate vaccine preparation, Dr. John C. Morrill (UTMB) for the MP-12 vaccine lot-7-2-88, and Dr. S. Widen at the UTMB Next Generation Sequencing Core for his technical guidance and NGS support. The authors also thank the anatomic pathology laboratory and the Animal Resources Center at UTMB for their technical supports. This study was supported by NIH R01 AI150917-01 (T.I.), as well as generous funding support from the Sealy Institute for Vaccine Sciences (SIVS) at UTMB.
Funding Information:
The authors thank Drs. A.B. Barrett, T.L. Brasel, and D.W.C. Beasley at The University of Texas Medical Branch at Galveston (UTMB) for their helpful discussion on RVF candidate vaccine preparation, Dr. John C. Morrill (UTMB) for the MP-12 vaccine lot-7-2-88, and Dr. S. Widen at the UTMB Next Generation Sequencing Core for his technical guidance and NGS support. The authors also thank the anatomic pathology laboratory and the Animal Resources Center at UTMB for their technical supports. This study was supported by NIH R01 AI150917-01 (T.I.), as well as generous funding support from the Sealy Institute for Vaccine Sciences (SIVS) at UTMB.
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.
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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 -