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Article Abstract
Alphaviruses are arthropod-borne viruses that cause widespread disease. However, many pathogenic alphaviruses are classified as risk group 3 human pathogens, which hampers the development of vaccines and therapeutic agents targeting alphavirus infections. In this study, we developed a RNA replication-defective Venezuelan equine encephalitis virus that has a complete nsP4 gene deletion (VEEV-△nsP4). A BHK cell line expressing nsP4 (BHK) was selected for trans-complementation to support the replication cycle of VEEV-△nsP4. The VEEV-△nsP4 only replicates in BHK cells and is immunologically similar to its parental wild type. Significantly, VEEV-△nsP4 is highly attenuated and a single dose immunization can protect mice from a lethal challenge. Furthermore, the RNA replication-defective vaccine strategy has been successfully employed for Chikungunya virus (CHIKV), Western equine encephalitis virus (WEEV) and Eastern equine encephalitis virus (EEEV). Overall, our study highlights the potential of the nsP4 trans-complementation system as a safe and effective platform for alphavirus vaccines development.
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| http://dx.doi.org/10.1016/j.ymthe.2025.08.051 | DOI Listing |
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