Department of Pediatrics, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand; Research Unit in Infectious and Immunology, Faculty of Medicine, Thammasat University, Pathumthani, Thailand; Clinical Research Center, Faculty of Medicine, Thammasat University, Pathumthani, Thailand.
Center of Excellence in Pediatric Infectious Diseases and Vaccines, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Vaccine. 2022 Apr 20;40(18):2551-2560. doi: 10.1016/j.vaccine.2022.03.036. Epub 2022 Mar 24.
Immunogenicity of inactivated SARS-CoV-2 vaccine has waning antibody over time. With the emergence of the SARS-CoV-2 delta variant, which requires higher neutralizing antibody to prevent infection, a booster dose is needed.
To evaluate immunogenicity and reactogenicity of standard- versus low-dose ChAdOx1 nCoV-19 vaccine booster after CoronaVac in healthy adults.
A double-blinded, randomized, controlled trial of adult, aged 18-59 years, with completion of 2-dose CoronaVac at 21-28 days apart for more than 2 months was conducted. Participants were randomized to receive AZD1222 (Oxford/AstraZeneca) intramuscularly; standard dose (SD, 5x10 viral particles) or low dose (LD, 2.5x10 viral particles). Surrogate virus neutralization test (sVNT) against wild type and delta variant, and anti-spike-receptor-binding-domain IgG (anti-S-RBD IgG) were compared as geometric mean ratio (GMR) at day 14 and 90 between LD and SD arms.
From July-August 2021, 422 adults with median age of 44 (IQR 36-51) years were enrolled. The median interval from CoronaVac to AZD1222 booster was 77 (IQR 64-95) days. At baseline, geometric means (GMs) of sVNT against delta variant and anti-S-RBD IgG were 18.1%inhibition (95% CI 16.4-20.0) and 111.5 (105.1-118.3) BAU/ml. GMs of sVNT against delta variant and anti-S-RBD IgG in SD were 95.6%inhibition (95% CI 94.3-97.0) and 1975.1 (1841.7-2118.2) BAU/ml at day 14, and 89.4%inhibition (86.4-92.4) and 938.6 (859.9-1024.4) BAU/ml at day 90, respectively. GMRs of sVNT against delta variant and anti-S-RBD IgG in LD compared to SD were 1.00 (95% CI 0.98-1.02) and 0.84 (0.76-0.93) at day 14, and 0.98 (0.94-1.03) and 0.89 (0.79-1.00) at day 90, respectively. LD recipients had significantly lower rate of fever (6.8% vs 25.0%) and myalgia (51.9% vs 70.7%) compared to SD.
Half-dose AZD1222 booster after 2-dose inactivated SARS-CoV-2 vaccination had non-inferior immunogenicity, yet lower systemic reactogenicity. Fractional low-dose AZD1222 booster should be considered especially in resource-constrained settings.
随着 SARS-CoV-2 德尔塔变异株的出现，预防感染所需的中和抗体水平更高，需要进行加强针接种。灭活 SARS-CoV-2 疫苗的抗体免疫原性会随时间推移而下降。
评估 CoronaVac 接种 2 剂后，使用标准剂量和低剂量 ChAdOx1 nCoV-19 疫苗加强剂对健康成年人的免疫原性和反应原性。
这是一项在成年人群中开展的、双盲、随机、对照试验，参与者年龄为 18-59 岁，2 剂 CoronaVac 的间隔为 21-28 天，且接种已超过 2 个月。参与者被随机分配接受 AZD1222（牛津/阿斯利康）肌肉注射；标准剂量（SD，5×10 病毒颗粒）或低剂量（LD，2.5×10 病毒颗粒）。在第 14 天和第 90 天，通过替代病毒中和试验（sVNT）比较野生型和 delta 变异株的中和抗体滴度以及抗刺突受体结合域 IgG（anti-S-RBD IgG）几何平均比（GMR）。
2021 年 7 月至 8 月，共纳入 422 名中位年龄为 44（IQR 36-51）岁的成年人。从 CoronaVac 到 AZD1222 加强针的中位间隔为 77（IQR 64-95）天。在基线时，delta 变异株 sVNT 和 anti-S-RBD IgG 的几何平均值（GM）分别为 18.1%抑制率（95%CI 16.4-20.0）和 111.5（105.1-118.3）BAU/ml。SD 组第 14 天 delta 变异株 sVNT 和 anti-S-RBD IgG 的 GM 分别为 95.6%抑制率（95%CI 94.3-97.0）和 1975.1（1841.7-2118.2）BAU/ml，第 90 天分别为 89.4%抑制率（86.4-92.4）和 938.6（859.9-1024.4）BAU/ml。与 SD 相比，LD 组第 14 天和第 90 天的 delta 变异株 sVNT 和 anti-S-RBD IgG 的 GMR 分别为 1.00（95%CI 0.98-1.02）和 0.84（0.76-0.93），0.98（0.94-1.03）和 0.89（0.79-1.00）。与 SD 相比，LD 组发热（6.8%比 25.0%）和肌痛（51.9%比 70.7%）的发生率显著较低。
在接种 2 剂灭活 SARS-CoV-2 疫苗后接种半剂量 AZD1222 加强针具有非劣效免疫原性，但全身反应原性较低。应考虑使用亚剂量 AZD1222 加强针，特别是在资源有限的环境中。
