ENSEMBLE COVID-19疫苗效力临床试验中单次Ad26.COV2.S剂量的免疫相关分析
Immune Correlates Analysis of a Single Ad26.COV2.S Dose in the ENSEMBLE COVID-19 Vaccine Efficacy Clinical Trial.
作者信息
Fong Youyi, McDermott Adrian B, Benkeser David, Roels Sanne, Stieh Daniel J, Vandebosch An, Gars Mathieu Le, Van Roey Griet A, Houchens Christopher R, Martins Karen, Jayashankar Lakshmi, Castellino Flora, Amoa-Awua Obrimpong, Basappa Manjula, Flach Britta, Lin Bob C, Moore Christopher, Naisan Mursal, Naqvi Muhammed, Narpala Sandeep, O'Connell Sarah, Mueller Allen, Serebryannyy Leo, Castro Mike, Wang Jennifer, Petropoulos Christos J, Luedtke Alex, Hyrien Ollivier, Lu Yiwen, Yu Chenchen, Borate Bhavesh, van der Laan Lars W P, Hejazi Nima S, Kenny Avi, Carone Marco, Wolfe Daniel N, Sadoff Jerald, Gray Glenda E, Grinsztejn Beatriz, Goepfert Paul A, Little Susan J, de Sousa Leonardo Paiva, Maboa Rebone, Randhawa April K, Andrasik Michele P, Hendriks Jenny, Truyers Carla, Struyf Frank, Schuitemaker Hanneke, Douoguih Macaya, Kublin James G, Corey Lawrence, Neuzil Kathleen M, Carpp Lindsay N, Follmann Dean, Gilbert Peter B, Koup Richard A, Donis Ruben O
机构信息
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
出版信息
medRxiv. 2022 Apr 12:2022.04.06.22272763. doi: 10.1101/2022.04.06.22272763.
Anti-spike IgG binding antibody, anti-receptor binding domain IgG antibody, and pseudovirus neutralizing antibody measurements four weeks post-vaccination were assessed as correlates of risk of moderate to severe-critical COVID-19 outcomes through 83 days post-vaccination and as correlates of protection following a single dose of Ad26.COV2.S COVID-19 vaccine in the placebo-controlled phase of ENSEMBLE, an international, randomized efficacy trial. Each marker had evidence as a correlate of risk and of protection, with strongest evidence for 50% inhibitory dilution (ID50) neutralizing antibody titer. The outcome hazard ratio was 0.49 (95% confidence interval 0.29, 0.81; p=0.006) per 10-fold increase in ID50; vaccine efficacy was 60% (43, 72%) at nonquantifiable ID50 (< 2.7 IU50/ml) and rose to 89% (78, 96%) at ID50 = 96.3 IU50/ml. Comparison of the vaccine efficacy by ID50 titer curves for ENSEMBLE-US, the COVE trial of the mRNA-1273 vaccine, and the COV002-UK trial of the AZD1222 vaccine supported consistency of the ID50 titer correlate of protection across trials and vaccine types.
在一项国际随机疗效试验ENSEMBLE的安慰剂对照阶段，评估了接种疫苗四周后抗刺突IgG结合抗体、抗受体结合域IgG抗体和假病毒中和抗体的测量结果，作为接种疫苗后83天内中度至重度-危重型COVID-19结局风险的相关因素，以及单剂Ad26.COV2.S COVID-19疫苗后保护作用的相关因素。每个标志物都有作为风险和保护相关因素的证据，其中50%抑制稀释度（ID50）中和抗体滴度的证据最为充分。ID50每增加10倍，结局风险比为0.49（95%置信区间0.29, 0.81；p=0.006）；在不可量化的ID50（<2.7 IU50/ml）时，疫苗效力为60%（43, 72%），在ID50 = 96.3 IU50/ml时升至89%（78, 96%）。对ENSEMBLE-US、mRNA-1273疫苗的COVE试验和AZD1222疫苗的COV002-UK试验按ID50滴度曲线进行的疫苗效力比较，支持了ID50滴度作为保护相关因素在不同试验和疫苗类型之间的一致性。
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