Single-shot AAV-vectored vaccine against SARS-CoV-2 with fast and long-lasting immunity

Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral...

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Main Authors: Fuhua Wu, Shuang Luo, Yongshun Zhang, Yangsen Ou, Hairui Wang, Zhaofei Guo, Chunting He, Shuting Bai, Penghui He, Min Jiang, Xiaoyan Chen, Guangsheng Du, Xun Sun
Format: Article
Language:English
Published: Elsevier 2023-05-01
Series:Acta Pharmaceutica Sinica B
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211383522003161
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author Fuhua Wu
Shuang Luo
Yongshun Zhang
Yangsen Ou
Hairui Wang
Zhaofei Guo
Chunting He
Shuting Bai
Penghui He
Min Jiang
Xiaoyan Chen
Guangsheng Du
Xun Sun
author_facet Fuhua Wu
Shuang Luo
Yongshun Zhang
Yangsen Ou
Hairui Wang
Zhaofei Guo
Chunting He
Shuting Bai
Penghui He
Min Jiang
Xiaoyan Chen
Guangsheng Du
Xun Sun
author_sort Fuhua Wu
collection DOAJ
description Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.
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spelling doaj.art-09a3494bedc844a8a47c7d85dbcee3812023-05-19T04:45:23ZengElsevierActa Pharmaceutica Sinica B2211-38352023-05-0113522192233Single-shot AAV-vectored vaccine against SARS-CoV-2 with fast and long-lasting immunityFuhua Wu0Shuang Luo1Yongshun Zhang2Yangsen Ou3Hairui Wang4Zhaofei Guo5Chunting He6Shuting Bai7Penghui He8Min Jiang9Xiaoyan Chen10Guangsheng Du11Xun Sun12Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaCorresponding author. Tel./fax: 86 28 85502307.; Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, ChinaDue to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines, the epidemic prevention and control are still challenging. Here, we employ a capsid and antigen structure engineering (CASE) strategy to manufacture an adeno-associated viral serotype 6-based vaccine (S663V-RBD), which expresses trimeric receptor binding domain (RBD) of spike protein fused with a biological adjuvant RS09. Impressively, the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months. Compared to the licensed BBIBP-CorV (Sinopharm, China), a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type, C.37 (Lambda) and B.1.617.2 (Delta). More interestingly, the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid. Given its effectiveness, the CASE-based S663V-RBD may provide a new solution for the current and next pandemic.http://www.sciencedirect.com/science/article/pii/S2211383522003161AAV vectorsCapsid engineeringVaccineAntigen structure designSARS-CoV-2
spellingShingle Fuhua Wu
Shuang Luo
Yongshun Zhang
Yangsen Ou
Hairui Wang
Zhaofei Guo
Chunting He
Shuting Bai
Penghui He
Min Jiang
Xiaoyan Chen
Guangsheng Du
Xun Sun
Single-shot AAV-vectored vaccine against SARS-CoV-2 with fast and long-lasting immunity
Acta Pharmaceutica Sinica B
AAV vectors
Capsid engineering
Vaccine
Antigen structure design
SARS-CoV-2
title Single-shot AAV-vectored vaccine against SARS-CoV-2 with fast and long-lasting immunity
title_full Single-shot AAV-vectored vaccine against SARS-CoV-2 with fast and long-lasting immunity
title_fullStr Single-shot AAV-vectored vaccine against SARS-CoV-2 with fast and long-lasting immunity
title_full_unstemmed Single-shot AAV-vectored vaccine against SARS-CoV-2 with fast and long-lasting immunity
title_short Single-shot AAV-vectored vaccine against SARS-CoV-2 with fast and long-lasting immunity
title_sort single shot aav vectored vaccine against sars cov 2 with fast and long lasting immunity
topic AAV vectors
Capsid engineering
Vaccine
Antigen structure design
SARS-CoV-2
url http://www.sciencedirect.com/science/article/pii/S2211383522003161
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