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

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

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

Author: Fuhua WU ¹ ; Shuang LUO ¹ ; Yongshun ZHANG ¹ ; Yangsen OU ¹ ; Hairui WANG ¹ ; Zhaofei GUO ¹ ; Chunting HE ¹ ; Shuting BAI ¹ ; Penghui HE ¹ ; Min JIANG ¹ ; Xiaoyan CHEN ¹ ; Guangsheng DU ¹ ; Xun SUN ¹
Author Information

1. 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, China.
Publication Type:Journal Article
Keywords: AAV vectors; Antigen structure design; Capsid engineering; SARS-CoV-2; Vaccine
From: Acta Pharmaceutica Sinica B 2023;13(5):2219-2233
CountryChina
Language:English
Abstract: 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.