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Chimeric mRNA-based COVID-19 vaccine induces protective immunity against Omicron and Delta variants.
Hu, Qidong; Zhao, Ying; Shaabani, Namir; Lyu, Xiaoxuan; Powers, Colin; Sun, Haotian; Cruz, Vincent; Stegman, Karen; Xu, Jia; Fossier, Amber; Huang, Yu; Ho, Giang; Kao, Yi; Wang, Zhihao; Wang, Zhenping; Hu, Yue; Zheng, Yi; Kyaw, Lilian; Zuluaga, Cipriano; Wang, Hua; Pei, Hong; Allen, Robert; Xie, Hui; Ji, Henry; Chen, Runqiang.
  • Hu Q; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Zhao Y; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Shaabani N; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Lyu X; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Powers C; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Sun H; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Cruz V; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Stegman K; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Xu J; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Fossier A; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Huang Y; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Ho G; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Kao Y; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Wang Z; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Wang Z; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Hu Y; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Zheng Y; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Kyaw L; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Zuluaga C; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Wang H; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Pei H; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Allen R; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Xie H; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Ji H; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
  • Chen R; Sorrento Therapeutics Inc., 4955 Directors Place, San Diego, CA 92121, USA.
Mol Ther Nucleic Acids ; 30: 465-476, 2022 Dec 13.
Article in English | MEDLINE | ID: covidwho-2211202
ABSTRACT
The emerging SARS-CoV-2 variants of concern (VOCs) exhibit enhanced transmission and immune escape, reducing the effectiveness of currently approved mRNA vaccines. To achieve wider coverage of VOCs, we first constructed a cohort of mRNAs harboring a furin cleavage mutation in the spike (S) protein of predominant VOCs, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2). The mutation abolished the cleavage between the S1 and S2 subunits. Systematic evaluation in vaccinated mice discovered that individual VOC mRNAs elicited strong neutralizing activity in a VOC-specific manner. In particular, the neutralizing antibodies (nAb) produced by immunization with Beta-Furin and Washington (WA)-Furin mRNAs showed potent cross-reactivity with other VOCs. However, neither mRNA elicited strong neutralizing activity against the Omicron variant. Hence, we further developed an Omicron-specific mRNA vaccine that restored protection against the original Omicron variant and some sublineages. Finally, to broaden the protection spectrum of the new Omicron mRNA vaccine, we engineered an mRNA-based chimeric immunogen by introducing the receptor-binding domain of Delta variant into the entire S antigen of Omicron. The resultant chimeric mRNA induced potent and broadly nAbs against Omicron and Delta, which paves the way to developing new vaccine candidates to target emerging variants in the future.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials / Systematic review/Meta Analysis Topics: Vaccines / Variants Language: English Journal: Mol Ther Nucleic Acids Year: 2022 Document Type: Article Affiliation country: J.omtn.2022.10.021

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials / Systematic review/Meta Analysis Topics: Vaccines / Variants Language: English Journal: Mol Ther Nucleic Acids Year: 2022 Document Type: Article Affiliation country: J.omtn.2022.10.021