The safety and efficacy of COVID-19 vaccines in the elderly, a high-risk group for severe COVID-19 infection, have not been fully understood. To clarify these issues, this prospective study followed up 157 elderly and 73 young participants for 16 months and compared the safety, immunogenicity, and efficacy of two doses of the inactivated vaccine BBIBP-CorV followed by a booster dose of the recombinant protein vaccine ZF2001. The results showed that this vaccination protocol was safe and tolerable in the elderly. After administering two doses of the BBIBP-CorV, the positivity rates and titers of neutralizing and anti-RBD antibodies in the elderly were significantly lower than those in the young individuals. After the ZF2001 booster dose, the antibody-positive rates in the elderly were comparable to those in the young; however, the antibody titers remained lower. Gender, age, and underlying diseases were independently associated with vaccine immunogenicity in elderly individuals. The pseudovirus neutralization assay showed that, compared with those after receiving two doses of BBIBP-CorV priming, some participants obtained immunological protection against BA.5 and BF.7 after receiving the ZF2001 booster. Breakthrough infection symptoms last longer in the infected elderly and pre-infection antibody titers were negatively associated with the severity of post-infection symptoms. The antibody levels in the elderly increased significantly after breakthrough infection but were still lower than those in the young. Our data suggest that multiple booster vaccinations at short intervals to maintain high antibody levels may be an effective strategy for protecting the elderly against COVID-19.

老年人是严重感染 COVID-19 的高危人群，COVID-19 疫苗在老年人中的安全性和有效性尚未得到充分了解。为了澄清这些问题，这项前瞻性研究对 157 名老年人和 73 名年轻参与者进行了为期 16 个月的随访，比较了两剂灭活疫苗 BBIBP-CorV 和加强剂量的重组蛋白疫苗 ZF2001 的安全性、免疫原性和有效性。结果表明，这种疫苗接种方案对于老年人来说是安全且可以耐受的。注射两剂BBIBP-CorV后，老年人中和抗体和抗RBD抗体的阳性率和滴度显着低于年轻人。 ZF2001加强剂量后，老年人的抗体阳性率与年轻人相当；然而，抗体滴度仍然较低。性别、年龄和基础疾病与老年人的疫苗免疫原性独立相关。假病毒中和试验显示，与接受两剂 BBIBP-CorV 初免后的参与者相比，一些参与者在接受 ZF2001 加强剂后获得了针对 BA.5 和 BF.7 的免疫保护。感染老年人的突破性感染症状持续时间更长，感染前抗体滴度与感染后症状的严重程度呈负相关。突破性感染后，老年人的抗体水平显着升高，但仍低于年轻人。我们的数据表明，短时间间隔多次加强疫苗接种以维持高抗体水平可能是保护老年人免受 COVID-19 感染的有效策略。