Replication Kinetics of a Candidate Live-Attenuated Vaccine for Cache Valley Virus in Aedes albopictus

Abstract

Background: The emergence or re-emergence of several orthobunyaviruses (order: Bunyavirales ; family: Peribunyaviridae ), including Cache Valley virus (CVV) and Oropouche virus, warrants the development and evaluation of candidate live-attenuated vaccines (LAVs). Ideally, these vaccines would elicit long-lasting immunity with one single immunization. Materials and Methods: Since the deletion of two virulence factors, NSs and NSm, has been shown to attenuate the virulence phenotype of orthobunyaviruses, phleboviruses, and nairoviruses, genetic manipulation of the viral genome is considered an effective strategy for the rational design of candidate LAVs for bunyaviruses across multiple families. In addition, the deletion of Rift Valley fever virus NSs and NSm genes has been shown to reduce transmission by mosquitoes. Results: In this study, the ability of a CVV mutant lacking the NSs and NSm genes (2delCVV) to replicate in intrathoracically injected Aedes albopictus was compared with the parental wild-type CVV (wtCVV) 6V633 strain. In contrast to the robust replication of wtCVV in injected mosquitoes, the multiplication kinetics of the 2delCVV mutant was reduced by more than a 100-fold. Conclusion: These results suggest that the deletion of NSm and NSs genes is a feasible approach to rationally design candidate orthobunyavirus LAVs that are highly attenuated in mosquitoes and, therefore, pose little risk of reversion to virulence and transmission.

Oropouche virus: A neglected global arboviral threat

“…Several strategies for vaccine development are being considered, including live attenuated, chemically inactivated, DNA-vectored, and protein-subunit immunization strategies ( Ayers et al., 2022 ). One of the most promising candidates is a live attenuated vaccine that has shown efficacy in animal models.…”

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

“…Recent advancements in animal models and vaccines such as the immunocompromised mouse model capable of eliciting in-utero disease similar to natural disease in sheep are advantageous for studying pathogenesis or vaccines because of its accessibility (Lopez et al 2021). 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.…”

“…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). While CVV outbreaks at farms cause large agroeconomic losses, the true direct and indirect costs have not been evaluated.…”