On Dec. 3rd, 2021, the Xiaoliang Xie Group and collaborators published a paper titled "Humoral immunogenicity and reactogenicity of CoronaVac or ZF2001 booster after two doses of inactivated vaccine" in Cell Research. This study provides urgently needed data support to the epidemic prevention and control policies.

　　At 4–8 months after primary immunization with CoronaVac, neutralizing antibody levels against the three variants are close to the lower limit of detection (8-fold dilution of plasma). Previous studies show that ZF2001, an RBD-subunit vaccine, could induce humoral immunity that exhibits better tolerance to current VOCs compared to inactivated vaccines and natural infections, suggesting ZF2001 as an ideal candidate for heterologous booster. To assess the impact of a third heterologous dose of ZF2001 or a third homologous dose of CoronaVac on vaccine-induced antibodies against VOCs, the researchers conducted a single-center, open-label, randomized controlled clinical trial among healthcare professionals at Beijing Ditan Hospital who had received two doses of CoronaVac in a 28-day interval 4–8 months earlier (Fig. S1). 

Fig. S1. Design of the clinical trial.

　　The researchers assessed the SARS-CoV-2 anti-spike IgG antibody levels and the geometric mean titers (GMTs) against authentic prototype SARS-CoV-2 and Beta, Gamma, and Delta variants on day 0 and 14 after administration of third doses for those vaccinated and for control group subjects. The third dose of either CoronaVac or ZF2001 vaccine rapidly induced a significantly high degree of humoral immunogenicity; the humoral immune response induced by ZF2001 was higher than that from CoronaVac(Fig. 1). Notably, both three-dose regimens were well tolerated. The most common adverse reactions were local injection site reactions, and all adverse reactions were grade 1.

　　Fig.1 Results of authentic virus neutralization assays using participants’ plasma against SARS-CoV-2 prototype strain (a), Beta strain (b), Gamma strain (c), and Delta strain (d). The geometric mean titer (GMT), geometric standard deviation, and pairwise fold-changes of 50% neutralization titers are labeled. HCS, human convalescent serum. Booster doses were administrated on Day 0. Statistical significances were analyzed by two-sided paired t-tests with log-transformation.

　　In the current pandemic situation with the Delta variant being predominant, analysis of the neutralizing capacity of vaccines against SARS-CoV-2 variants is of utmost relevance. The results suggest that heterologous boosters, such as RBD subunit vaccines, may also contribute to protecting SARS-CoV-2 symptomatic illness and maybe more efficient against VOCs. 

　　Yunlong Cao, Xiaohua Hao, Xi Wang, and Qianhui Wu are the co-first authors of the paper. Yunlong Cao, Hongjie Yu, Xiaoliang Sunney Xie, and Ronghua Jin are the co-corresponding authors of the paper. This project is financially supported by the Ministry of Science and Technology of China (CPL-1233).