Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Adelson School of Medicine, Ariel University, Ariel, Israel; Schneider Children's Medical Center, Petach Tikva, Israel.
Clin Microbiol Infect. 2023 Mar;29(3):366-371. doi: 10.1016/j.cmi.2022.10.011. Epub 2022 Oct 13.
Establishing a correlate of protection is essential for the development and licensure of Shigella vaccines. We examined potential threshold levels of serum IgG to Shigella lipopolysaccharide (LPS) that could predict protection against shigellosis.
We performed new analyses of serologic and vaccine efficacy (VE) data from two randomized vaccine-controlled trials of the Shigella sonnei-Pseudomonas aeruginosa recombinant exoprotein A (rEPA) conjugate conducted in young adults and children aged 1-4 years in Israel. Adults received either S. sonnei-rEPA (n = 183) or control vaccines (n = 277). Children received the S. sonnei-rEPA conjugate (n = 1384) or S. flexneri 2a-rEPA conjugate (n = 1315). VE against culture-proven shigellosis was determined. Sera were tested for IgG anti-S. sonnei LPS antibodies. We assessed the association of various levels of IgG anti-S. sonnei LPS antibodies with S. sonnei shigellosis risk using logistic regression models and the reverse cumulative distribution of IgG levels.
Among adults, four vaccinees and 23 controls developed S. sonnei shigellosis; the VE was 74% (95% CI, 28-100%). A threshold of ≥1:1600 IgG anti-S. sonnei LPS titre was associated with a reduced risk of S. sonnei shigellosis and a predicted VE of 73.6% (95% CI, 65-80%). The IgG anti-S. sonnei LPS correlated with serum bactericidal titres. In children, a population-based level of 4.5 ELISA Units (EU) corresponding to 1:1072 titre, predicted VE of 63%, versus 71% observed VE in children aged 3-4 years. The predicted VE in children aged 2-4 years was 49%, consistent with the 52% observed VE.
Serum IgG anti-S. sonnei LPS threshold levels can predict the degree of VE and can be used for the evaluation of new vaccine candidates.
建立保护相关物对于志贺氏菌疫苗的开发和许可至关重要。我们研究了血清志贺氏菌脂多糖（LPS）IgG 的潜在阈值水平，该水平可能预测对志贺氏菌病的保护作用。
我们对两项在以色列进行的针对年轻人和 1-4 岁儿童的志贺氏菌 sonnei-Pseudomonas aeruginosa 重组外蛋白 A（rEPA）结合物的随机疫苗对照试验的血清学和疫苗功效（VE）数据进行了新的分析。成年人接受了 S. sonnei-rEPA（n=183）或对照疫苗（n=277）。儿童接受了 S. sonnei-rEPA 结合物（n=1384）或 S. flexneri 2a-rEPA 结合物（n=1315）。通过培养确定了针对文化证实的志贺氏菌病的 VE。检测血清 IgG 抗 S. sonnei LPS 抗体。我们使用逻辑回归模型和 IgG 水平的反向累积分布评估了各种 IgG 抗 S. sonnei LPS 抗体水平与 S. sonnei 志贺氏菌病风险的关联。
在成年人中，4 名疫苗接种者和 23 名对照者发生了 S. sonnei 志贺氏菌病；VE 为 74%（95%CI，28-100%）。≥1:1600 IgG 抗 S. sonnei LPS 效价与 S. sonnei 志贺氏菌病风险降低相关，预测 VE 为 73.6%（95%CI，65-80%）。IgG 抗 S. sonnei LPS 与血清杀菌滴度相关。在儿童中，与观察到的 VE 为 71%的 3-4 岁儿童相比，基于人群的 4.5 ELISA 单位（EU）相当于 1:1072 效价，预测 VE 为 63%。在 2-4 岁儿童中，预测 VE 为 49%，与观察到的 52% VE 一致。
血清 IgG 抗 S. sonnei LPS 阈值水平可以预测 VE 的程度，并可用于评估新的疫苗候选物。
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