A chimeric adenovirus-vectored vaccine based on Beta spike and Delta RBD confers a broad-spectrum neutralization against Omicron-included SARS-CoV-2 variants

doi:10.1002/mco2.539

MedComm ›› 2024, Vol. 5 ›› Issue (5) : e539. DOI: 10.1002/mco2.539

Weiqi Hong¹, Hong Lei¹, Dandan Peng¹, Yuhe Huang¹, Cai He¹, Jingyun Yang¹, Yanan Zhou², Jian Liu¹, Xiangyu Pan¹, Haiying Que¹, Aqu Alu¹, Li Chen¹, Jiayuan Ai¹, Furong Qin¹, Binhan Wang¹, Danyi Ao¹, Zhen Zeng¹, Ying Hao¹, Yu Zhang¹, Xiya Huang¹, Chunjun Ye¹, MinYang Fu¹, Xuemei He¹, Zhenfei Bi¹, Xuejiao Han¹, Min Luo¹, Hongbo Hu¹, Wei Cheng¹, Haohao Dong¹, Jian Lei¹, Lu Chen¹, Xikun Zhou¹, Wei Wang¹, Guangwen Lu¹, Guobo Shen¹, Li Yang¹, Jinliang Yang¹, Jiong Li¹, Zhenling Wang¹, Xiangrong Song¹, Qiangming Sun²(), Shuaiyao Lu²(), Youchun Wang²(), Ping Cheng¹(), Xiawei Wei¹()

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Abstract

Urgent 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 (T_RM) 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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adenovirus / broad-spectrum neutralization / intranasal vaccine / SARS-CoV-2

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Weiqi Hong, Hong Lei, Dandan Peng, Yuhe Huang, Cai He, Jingyun Yang, Yanan Zhou, Jian Liu, Xiangyu Pan, Haiying Que, Aqu Alu, Li Chen, Jiayuan Ai, Furong Qin, Binhan Wang, Danyi Ao, Zhen Zeng, Ying Hao, Yu Zhang, Xiya Huang, Chunjun Ye, MinYang Fu, Xuemei He, Zhenfei Bi, Xuejiao Han, Min Luo, Hongbo Hu, Wei Cheng, Haohao Dong, Jian Lei, Lu Chen, Xikun Zhou, Wei Wang, Guangwen Lu, Guobo Shen, Li Yang, Jinliang Yang, Jiong Li, Zhenling Wang, Xiangrong Song, Qiangming Sun, Shuaiyao Lu, Youchun Wang, Ping Cheng, Xiawei Wei. A chimeric adenovirus-vectored vaccine based on Beta spike and Delta RBD confers a broad-spectrum neutralization against Omicron-included SARS-CoV-2 variants. MedComm, 2024, 5(5): e539 https://doi.org/10.1002/mco2.539

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