Comparison of Immunogenicity Between a Candidate Live Attenuated Vaccine and an Inactivated Vaccine for Cache Valley Virus

Abstract

Cache Valley virus (CVV) is a mosquito-borne bunyavirus that is enzootic throughout the new world. Although CVV is known as an important agricultural pathogen, primarily associated with embryonic lethality and abortions in ruminants, it has recently been recognized for its expansion as a zoonotic pathogen. With the increased emergence of bunyaviruses with human and veterinary importance, there have been significant efforts dedicated to the development of bunyavirus vaccines. In this study, the immunogenicity of a candidate live-attenuated vaccine (LAV) for CVV, which contains the deletion of the nonstructural small (NSs) and nonstructural medium (NSm) genes (2delCVV), was evaluated and compared with an autogenous candidate vaccine created through the inactivation of CVV using binary ethylenimine (BEI) with an aluminum hydroxide adjuvant (BEI-CVV) in sheep. Both 2delCVV and BEI-CVV produced a neutralizing antibody response that exceeds the correlate of protection, that is, plaque reduction neutralization test titer >10. However, on day 63 postinitial immunization, 2delCVV was more immunogenic than BEI-CVV. These results warrant further development of 2delCVV as a candidate LAV and demonstrate that the double deletion of the NSs and NSm genes can be applied to the development of vaccines and as a common attenuation strategy for orthobunyaviruses.

Cache Valley virus: an emerging arbovirus of public and veterinary health importance

“…To study CVV vaccine efficacy, 6-month-old male Rambouillet lambs were used to determine immunogenicity of a candidate live-attenuated CVV vaccine and were shown to produce a neutralizing antibody response after vaccination. Challenge experiments were not conducted as CVV does not cause clinical symptoms in adult ruminants, demonstrating that an ovine model to study vaccine efficacy in pregnant ewes would be useful (Ayers et al 2023).…”

“…Recent research on vaccine development has described the creation of a live-attenuated CVV vaccine candidate that lacks both nonstructural proteins (NSs and NSm) (Ayers et al 2022). Presently, a lack of transmissibility in mosquitoes by the deletion mutant virus and immunogenicity was demonstrated (Ayers et al 2023); however, protective efficacy has not been investigated. To understand the benefit of vaccination, the economic impact of CVV disease must be understood, but no such studies have been conducted (Waddell et al 2019, Ayers et al 2022).…”