Mary Wilson
Well-known member
Published: 14 December 2022
DOI https://doi.org/10.1038/s41392-022-01246-x
Hong-Qing Zhang, Ya-Nan Zhang, Zhe-Rui Zhang, Xiao-Ling Chen, Yan-Yan Hu, Yu-Jia Shi, Jing Wang, Cheng-lin Deng, Bo Zhang, Xiao-Dan Li & Han-Qing Ye
Dear Editor,
The prolonged outbreak and spread of coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 poses a great threat to global economic and public health. The protective efficacy of the vaccines based on the spike protein (S) of SARS-CoV-2 has been compromised by the emergence of variants of concern (VOC). The Omicron variant which is designated as the fifth VOC by WHO, has rapidly replaced the Delta variant as the dominant variant worldwide since its emergence in November 2021 in South Africa. The Omicron variant carries more than 30 mutations/deletions/insertion in the S protein as well as the receptor binding domain (RBD). Accumulated evidence has demonstrated that the Omicron variant can largely escape from vaccination, convalescent sera, and most of the approved therapeutic monoclonal antibodies,[SUP]1[/SUP] posing a high risk of infection and reinfection in highly vaccinated populations. Thus, a targeted vaccine against the Omicron is crucial to contain the spread of the variant.
In this study, we generated a SARS-CoV-2 Omicron variant vaccine using Venezuelan equine encephalitis virus (VEEV) replicon to encode the prefusion-stabilized spike protein of the Omicron variant BA.1. VEEV is a positive-sense, single-stranded RNA virus that belongs to the genus alphavirus of the family Togaviridae. Compared with the conventional non-replicating mRNA, the alphavirus-derived self-amplifying replicon RNA (saRNA) encodes the viral replicase as well as a gene of interest (GOI), which enables the RNA replication and GOI expression in the cytoplasm[SUP]2[/SUP] and circumvents the risk of genomic integration, thus enhances the safety profile of the saRNA-based vaccines. Additionally, the replicable saRNA could activate an innate immune response, which has the potential to provide an adjuvant effect on vaccine potency. The replicon could be encapsulated into single-round infectious alphavirus replicon particles (VRPs) by in trans supplement of the viral structural proteins and thereafter be delivered into cells by VRP infection.[SUP]2[/SUP] The alphavirus VRP system has been extensively used in cancer therapy and vaccine development with well-demonstrated safety and tolerability in numerous clinical trials.[SUP]2
...
https://www.nature.com/articles/s41392-022-01246-x#citeas[/SUP]
DOI https://doi.org/10.1038/s41392-022-01246-x
Hong-Qing Zhang, Ya-Nan Zhang, Zhe-Rui Zhang, Xiao-Ling Chen, Yan-Yan Hu, Yu-Jia Shi, Jing Wang, Cheng-lin Deng, Bo Zhang, Xiao-Dan Li & Han-Qing Ye
Dear Editor,
The prolonged outbreak and spread of coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 poses a great threat to global economic and public health. The protective efficacy of the vaccines based on the spike protein (S) of SARS-CoV-2 has been compromised by the emergence of variants of concern (VOC). The Omicron variant which is designated as the fifth VOC by WHO, has rapidly replaced the Delta variant as the dominant variant worldwide since its emergence in November 2021 in South Africa. The Omicron variant carries more than 30 mutations/deletions/insertion in the S protein as well as the receptor binding domain (RBD). Accumulated evidence has demonstrated that the Omicron variant can largely escape from vaccination, convalescent sera, and most of the approved therapeutic monoclonal antibodies,[SUP]1[/SUP] posing a high risk of infection and reinfection in highly vaccinated populations. Thus, a targeted vaccine against the Omicron is crucial to contain the spread of the variant.
In this study, we generated a SARS-CoV-2 Omicron variant vaccine using Venezuelan equine encephalitis virus (VEEV) replicon to encode the prefusion-stabilized spike protein of the Omicron variant BA.1. VEEV is a positive-sense, single-stranded RNA virus that belongs to the genus alphavirus of the family Togaviridae. Compared with the conventional non-replicating mRNA, the alphavirus-derived self-amplifying replicon RNA (saRNA) encodes the viral replicase as well as a gene of interest (GOI), which enables the RNA replication and GOI expression in the cytoplasm[SUP]2[/SUP] and circumvents the risk of genomic integration, thus enhances the safety profile of the saRNA-based vaccines. Additionally, the replicable saRNA could activate an innate immune response, which has the potential to provide an adjuvant effect on vaccine potency. The replicon could be encapsulated into single-round infectious alphavirus replicon particles (VRPs) by in trans supplement of the viral structural proteins and thereafter be delivered into cells by VRP infection.[SUP]2[/SUP] The alphavirus VRP system has been extensively used in cancer therapy and vaccine development with well-demonstrated safety and tolerability in numerous clinical trials.[SUP]2
...
https://www.nature.com/articles/s41392-022-01246-x#citeas[/SUP]
