Heterologous Prime-boost with Chimpanzee Adenovirus Vector and Receptor-Binding Domain Recombinant Subunit Protein COVID-19 Vaccine Induces Strong Immune Responses in Mice

Author(s): Qinhua Peng, Xiaohong Wu, Xingxing Li, Zelun Zhang, Hongshan Xu, Xinyu Liu, Wenjuan Li, Miao Li, Enyue Fang, Xiaohui Liu, Jingjing Liu, Danhua Zhao, Lihong Yang, Hongyu Wang, Jia Li, Yanqiu Huang, Leitai Shi, Yunpeng Wang, Ren Yang, Guangzhi Yue, Yue Suo, Min Li, Shouchun Cao, Qiang Ye and Yuhua Li

Several vaccines for coronavirus disease 2019 have been developed worldwide. A heterologous prime-boost strategy has been identified as a potential method for achieving potent immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, by adopting pathogen-free, female BALB/c mice, the present work assessed diverse prime-boosted strategies using the chimpanzee adenovirus vector-based vaccine, ChAdTS-S (ChAd), together with the recombinant subunit vaccine, ZF2001. Animals were divided into 12 groups (n = 5 per group) for immunization according to the corresponding immunization procedures. ChAd was given through intranasal (i.n.) or intramuscular (i.m.) administration, while ZF2001 through i.m. administration. At 42 days after primary immunization, the highest specific pseudovirus-neutralizing antibody (PNAb) and IgG levels against the Wuhan-Hu-1 strain were induced in the heterologous prime-boost group (i.m. ChAd > i.m. ZF2001 group) among all the different vaccination combination groups. In addition, the i.n.-administered ChAd group induced higher PNAb to resist the Wuhan-Hu-1 strain in comparison with the i.m.-administered ChAd group. All vaccination groups exhibited low vaccine-induced PNAb levels to resist the B.1.1.529 strain. Higher IgA levels were induced in the i.n. vaccination-containing groups. The i.m. ZF2001 > i.n. ChAd strategy exhibited the highest angiotensin-converting enzyme-2-binding inhibition level for resisting diverse SARS-CoV-2 variants. All vaccinations triggered Th1-biased cellular immunity. Among these, the i.m.-administered ChAd strategy induced higher levels of Th1 cytokines compared to those induced with i.n.-administered ChAd. This study provides reference data for optimizing the heterologous prime-boost vaccination strategy against COVID-19.