Heterologous Prime-boost Immunisation with AdC68 and mRNA-based COVID-19 Vaccine Induced Strong and Durable Immune Responses in Mice

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

Immune escape events caused by the emergence of new variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continue to increase. The heterologous prime-boost immunisation strategy can improve the efficacy of vaccine protection. However, the persistent immune response after vaccination has rarely been investigated. In this study, we evaluated the immunogenicity of heterologous prime-boost protocols using the AdC68-based vaccine ChAdTS-S (Ad) and mRNA-based vaccine ARCoV (AR). Different groups of 4-week-old BALB/c mice were administered heterologous prime-boost or homologous prime-boost of Ad and AR, along with blank control phosphate-buffered saline vaccinations. We evaluated the immune response trend in these mice from 8 to 57 weeks after prime immunisation. Intranasal priming with Ad followed by an intramuscular booster with AR induced strong and durable humoral and local mucosal immune responses in all vaccination groups. The groups exhibited high IgG, IgA, and pseudovirus neutralising antibody titres and ACE2 binding inhibition from weeks 8 to 57 after prime vaccination. All Ad and AR vaccination groups showed a Th1-skewing cellular immune response. In conclusion, this study provides data to support coronavirus disease 2019 vaccination strategies and the existence of persistent immunity.