A chimeric adenovirus‐vectored vaccine based on Beta spike and Delta RBD confers a broad‐spectrum neutralization against Omicron‐included SARS‐CoV‐2 variants
Author:
Hong Weiqi1ORCID, Lei Hong1, Peng Dandan1ORCID, Huang Yuhe1, He Cai1, Yang Jingyun1, Zhou Yanan2, Liu Jian1, Pan Xiangyu1, Que Haiying1, Alu Aqu1, Chen Li1, Ai Jiayuan1, Qin Furong1, Wang Binhan1, Ao Danyi1ORCID, Zeng Zhen1, Hao Ying1, Zhang Yu1, Huang Xiya1, Ye Chunjun1, Fu MinYang1, He Xuemei1, Bi Zhenfei1ORCID, Han Xuejiao1, Luo Min1, Hu Hongbo1, Cheng Wei1, Dong Haohao1, Lei Jian1, Chen Lu1, Zhou Xikun1ORCID, Wang Wei1, Lu Guangwen1, Shen Guobo1, Yang Li1, Yang Jinliang1, Li Jiong1, Wang Zhenling1, Song Xiangrong1, Sun Qiangming2, Lu Shuaiyao2, Wang Youchun2, Cheng Ping1, Wei Xiawei1ORCID
Affiliation:
1. Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer Center National Clinical Research Center for Geriatrics West China Hospital Sichuan University Chengdu Sichuan China 2. National Kunming High‐level Biosafety Primate Research Center Institute of Medical Biology Chinese Academy of Medical Sciences and Peking Union Medical College Kunming Yunnan China
Abstract
AbstractUrgent research into innovative severe acute respiratory coronavirus‐2 (SARS‐CoV‐2) vaccines that may successfully prevent various emerging emerged variants, particularly the Omicron variant and its subvariants, is necessary. Here, we designed a chimeric adenovirus‐vectored vaccine named Ad5‐Beta/Delta. This vaccine was created by incorporating the receptor‐binding domain from the Delta variant, which has the L452R and T478K mutations, into the complete spike protein of the Beta variant. Both intramuscular (IM) and intranasal (IN) vaccination with Ad5‐Beta/Deta vaccine induced robust broad‐spectrum neutralization against Omicron BA.5‐included variants. IN immunization with Ad5‐Beta/Delta vaccine exhibited superior mucosal immunity, manifested by higher secretory IgA antibodies and more tissue‐resident memory T cells (TRM) in respiratory tract. The combination of IM and IN delivery of the Ad5‐Beta/Delta vaccine was capable of synergically eliciting stronger systemic and mucosal immune responses. Furthermore, the Ad5‐Beta/Delta vaccination demonstrated more effective boosting implications after two dosages of mRNA or subunit recombinant protein vaccine, indicating its capacity for utilization as a booster shot in the heterologous vaccination. These outcomes quantified Ad5‐Beta/Delta vaccine as a favorable vaccine can provide protective immunity versus SARS‐CoV‐2 pre‐Omicron variants of concern and BA.5‐included Omicron subvariants.
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