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:10.1038/s41541-022-00536-3

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

NPJ Vaccines. 2022 Sep 21;7(1):109. doi: 10.1038/s41541-022-00536-3.

Authors

Tetsuro Ikegami^{1

2

3}, Eduardo Jurado-Cobena⁴, Cigdem Alkan⁵, Jennifer K Smith⁵, Lihong Zhang⁵, Birte Kalveram⁵, Terry L Juelich⁵, Allen T Esterly^{6

7

8}, Jahnavi R Bhaskar^{6

7

8}, Saravanan Thangamani^{6

7

8}, Alexander N Freiberg^{5

9

10}

Affiliations

¹ Department of Pathology, The University of Texas Medical Branch at Galveston, 301 University Blvd, Galveston, TX, 77555, USA. teikegam@utmb.edu.
² The Sealy Institute for Vaccine Sciences, The University of Texas Medical Branch at Galveston, 301 University Blvd, Galveston, TX, 77555, USA. teikegam@utmb.edu.
³ The Center for Biodefense and Emerging Infectious Diseases, The University of Texas Medical Branch at Galveston, 301 University Blvd, Galveston, TX, 77555, USA. teikegam@utmb.edu.
⁴ Department of Microbiology and Immunology, The University of Texas Medical Branch at Galveston, 301 University Blvd, Galveston, TX, 77555, USA.
⁵ Department of Pathology, The University of Texas Medical Branch at Galveston, 301 University Blvd, Galveston, TX, 77555, USA.
⁶ Department of Microbiology and Immunology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
⁷ SUNY Center for Vector-Borne Diseases, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
⁸ Institute for Global Health and Translational Science, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
⁹ The Sealy Institute for Vaccine Sciences, The University of Texas Medical Branch at Galveston, 301 University Blvd, Galveston, TX, 77555, USA.
¹⁰ The Center for Biodefense and Emerging Infectious Diseases, The University of Texas Medical Branch at Galveston, 301 University Blvd, Galveston, TX, 77555, USA.

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.

Abstract

Grants and funding