tetano
Editor, Senior Moderator
Sci Adv
. 2025 Sep 26;11(39):eadx7487.
doi: 10.1126/sciadv.adx7487. Epub 2025 Sep 26. Development of SARS-CoV-2 as a viral vector: A novel intranasal bivalent vaccine for SARS-CoV-2 and RSV
Jiayu Xu[SUP] 1 [/SUP], Michelle Chamblee[SUP] 1 [/SUP], Fei Jiang[SUP] 1 [/SUP], Mahesh Kc[SUP] 2 [/SUP], Cheng Chih Hsu[SUP] 1 [/SUP], Ilada Thongpan[SUP] 2 [/SUP], Phylip Chen[SUP] 2 [/SUP], Yuexiu Zhang[SUP] 1 [/SUP], Chun-Ta Chiu[SUP] 1 [/SUP], Mohamed M Shamseldin[SUP] 3 [/SUP], Heba M Amer[SUP] 3 [/SUP], Xueya Liang[SUP] 1 [/SUP], Amal O Amer[SUP] 3 4 [/SUP], Prosper N Boyaka[SUP] 1 [/SUP], Estelle Cormet-Boyaka[SUP] 1 [/SUP], Mark E Peeples[SUP] 2 4 5 [/SUP], Jianrong Li[SUP] 1 4 6 [/SUP]
Affiliations
Negative-sense RNA viruses have been widely used as viral vectors for vaccine delivery. However, little is known about coronaviruses as vectors for delivering vaccines. Here, we have developed safe SARS-CoV-2 Omicron JN.1-based live attenuated vaccine candidates by combining a mutation (D130A) in the viral nsp16 protein, deletion of the furin cleavage site (dFCS) in the spike protein, deletion of accessory proteins, and/or modification of the transcription regulatory sequences (mTRS). Subsequently, using rJN.1, rJN.1-D130A-dFCS, and rJN.1-mTRS-D130A-dFCS as the backbones, we generated three recombinant viruses expressing a nonfunctional, soluble, and stabilized prefusion F protein of human respiratory syncytial virus (RSVF). Among them, rJN.1-D130A-dFCS-RSVF virus was sufficiently attenuated and highly immunogenic, providing complete protection against challenge with both JN.1 and RSV in hamsters. However, rJN.1-mTRS-D130A-dFCS-RSVF was poorly immunogenic. Collectively, we demonstrate that attenuated SARS-CoV-2 is an effective viral vector for delivering RSV vaccine, warranting further development as a novel intranasal bivalent vaccine for SARS-CoV-2 and RSV.
. 2025 Sep 26;11(39):eadx7487.
doi: 10.1126/sciadv.adx7487. Epub 2025 Sep 26. Development of SARS-CoV-2 as a viral vector: A novel intranasal bivalent vaccine for SARS-CoV-2 and RSV
Jiayu Xu[SUP] 1 [/SUP], Michelle Chamblee[SUP] 1 [/SUP], Fei Jiang[SUP] 1 [/SUP], Mahesh Kc[SUP] 2 [/SUP], Cheng Chih Hsu[SUP] 1 [/SUP], Ilada Thongpan[SUP] 2 [/SUP], Phylip Chen[SUP] 2 [/SUP], Yuexiu Zhang[SUP] 1 [/SUP], Chun-Ta Chiu[SUP] 1 [/SUP], Mohamed M Shamseldin[SUP] 3 [/SUP], Heba M Amer[SUP] 3 [/SUP], Xueya Liang[SUP] 1 [/SUP], Amal O Amer[SUP] 3 4 [/SUP], Prosper N Boyaka[SUP] 1 [/SUP], Estelle Cormet-Boyaka[SUP] 1 [/SUP], Mark E Peeples[SUP] 2 4 5 [/SUP], Jianrong Li[SUP] 1 4 6 [/SUP]
Affiliations
- PMID: 41004586
- PMCID: PMC12466924
- DOI: 10.1126/sciadv.adx7487
Negative-sense RNA viruses have been widely used as viral vectors for vaccine delivery. However, little is known about coronaviruses as vectors for delivering vaccines. Here, we have developed safe SARS-CoV-2 Omicron JN.1-based live attenuated vaccine candidates by combining a mutation (D130A) in the viral nsp16 protein, deletion of the furin cleavage site (dFCS) in the spike protein, deletion of accessory proteins, and/or modification of the transcription regulatory sequences (mTRS). Subsequently, using rJN.1, rJN.1-D130A-dFCS, and rJN.1-mTRS-D130A-dFCS as the backbones, we generated three recombinant viruses expressing a nonfunctional, soluble, and stabilized prefusion F protein of human respiratory syncytial virus (RSVF). Among them, rJN.1-D130A-dFCS-RSVF virus was sufficiently attenuated and highly immunogenic, providing complete protection against challenge with both JN.1 and RSV in hamsters. However, rJN.1-mTRS-D130A-dFCS-RSVF was poorly immunogenic. Collectively, we demonstrate that attenuated SARS-CoV-2 is an effective viral vector for delivering RSV vaccine, warranting further development as a novel intranasal bivalent vaccine for SARS-CoV-2 and RSV.