Liu Wenqing, Li Yuqing, Li Xiaolong, Wang Feiyu, Qi Runjie, Zhu Tao, Li Jingxin
School of Public Health, National Vaccine Innovation Platform, Nanjing Medical University, Nanjing 211166, China.
CanSino Biologics Inc., Tianjin 300457, China.
Vaccines (Basel). 2025 Mar 20;13(3):333. doi: 10.3390/vaccines13030333.
: Pre-existing adenovirus immunity restricts the utilization of adenovirus-vectored vaccines. The current study aims to conduct a pooled analysis of eight clinical trials to evaluate the influence of pre-existing Ad5 neutralizing antibodies on immunogenicity of Ad5-nCoV. : The primary outcome indicator of this pooled analysis is the geometric mean titers (GMTs) of live SARS-CoV-2 NAbs against the wild-type strain on day 28 post-vaccination. Participants were divided into two cohorts: an adolescent cohort comprising individuals aged 6-17 years and an adult cohort with individuals aged 18 years and older. Within each cohort, individuals were further categorized into three subgroups based on their Ad5-nCoV vaccination schedules: one subgroup received a single intramuscular dose as the primary regimen (Ad5-IM-prime), another received an intramuscular dose as the heterologous prime-boost regimen (Ad5-IM-boost), and the last subgroup received an aerosolized dose as the heterologous prime-boost regimen (Ad5-IH-boost). : A total of 3512 participants were included in this pooled analysis. In the Ad5-IM-prime subgroup, there were 1001 adolescents and 1450 adults; in the Ad5-IM-boost subgroup, there were 65 adolescents and 396 adults; and in the Ad5-IH-boost subgroup, there were 207 adolescents and 393 adults. In the adult cohort, the GMTs of NAbs against wild-type SARS-CoV-2 on day 28 post-vaccination for the Ad5-IM-prime, Ad5-IM-boost, and Ad5-IH-boost subgroups were 35.6 (95% CI: 32.0, 39.7), 358.3 (95% CI: 267.6, 479.6), and 2414.1 (95% CI: 2006.9, 2904.0), respectively, with negative (less than 1:12) pre-existing NAb titers compared to 10.7 (95% CI: 9.1, 12.6), 116.9 (95% CI: 84.9, 161.1), and 762.7 (95% CI: 596.2, 975.8), respectively, with high (greater than 1:1000) pre-existing NAb titers. A similar trend was observed in the adolescent cohort, where pre-existing immunity was found to reduce the peak of live SARS-CoV-2 Nabs post-vaccination. : Regardless of whether Ad5-nCoV is administered as a primary vaccination regimen or as a heterologous prime-boost strategy, a negative impact on immunogenicity can still be observed in the presence of high pre-existing immunity. However, when primary immunization is achieved with inactivated COVID-19 vaccines, aerosol inhalation can significantly enhance the immunogenicity of Ad5-nCoV compared to intramuscular injections of Ad5-nCoV as a booster.
预先存在的腺病毒免疫力会限制腺病毒载体疫苗的使用。当前研究旨在对八项临床试验进行汇总分析，以评估预先存在的Ad5中和抗体对Ad5-nCoV免疫原性的影响。：这项汇总分析的主要结果指标是接种疫苗后第28天针对野生型毒株的活SARS-CoV-2中和抗体的几何平均滴度（GMT）。参与者分为两个队列：一个是年龄在6至17岁的青少年队列，另一个是年龄在18岁及以上的成人队列。在每个队列中，个体根据其Ad5-nCoV疫苗接种方案进一步分为三个亚组：一个亚组接受单次肌肉注射作为主要方案（Ad5-IM-prime），另一个接受肌肉注射作为异源初免-加强方案（Ad5-IM-boost），最后一个亚组接受雾化剂量作为异源初免-加强方案（Ad5-IH-boost）。：共有3512名参与者纳入了这项汇总分析。在Ad5-IM-prime亚组中，有1001名青少年和1450名成人；在Ad5-IM-boost亚组中，有65名青少年和396名成人；在Ad5-IH-boost亚组中，有207名青少年和393名成人。在成人队列中，Ad5-IM-prime、Ad5-IM-boost和Ad5-IH-boost亚组在接种疫苗后第28天针对野生型SARS-CoV-2的中和抗体GMT分别为35.6（95%CI：32.0，39.7）、358.3（95%CI：267.6，479.6）和2414.1（95%CI：2006.9，2904.0），预先存在的中和抗体滴度为阴性（小于1:12），而预先存在的中和抗体滴度高（大于1:1000）时，分别为10.7（95%CI：9.1，12.6）、116.9（95%CI：84.9，161.1）和762.7（95%CI：596.2，975.8）。在青少年队列中也观察到了类似趋势，发现预先存在的免疫力会降低接种疫苗后活SARS-CoV-2中和抗体的峰值。：无论Ad5-nCoV是作为主要疫苗接种方案还是作为异源初免-加强策略给药，在预先存在高免疫力的情况下，仍可观察到对免疫原性的负面影响。然而，当用灭活的COVID-19疫苗进行初次免疫时，与肌肉注射Ad5-nCoV作为加强针相比，雾化吸入可显著增强Ad5-nCoV的免疫原性。
