The effect of immunization schedule with the malaria vaccine candidate RTS,S/AS01E on protective efficacy and anti-circumsporozoite protein antibody avidity in African infants
The effect of immunization schedule with the malaria vaccine candidate RTS,S/AS01E on protective efficacy and anti-circumsporozoite protein antibody avidity in African infants
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DOI：
10.1186/s12936-015-0605-7
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发表时间：
2015-02-13
期刊：
影响因子：
3
通讯作者：
Mordmueller, Benjamin
中科院分区：
文献类型：
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作者：
Ajua, Anthony;Lell, Bertrand;Mordmueller, Benjamin
背景：疟疾疫苗 RTS,S 诱导针对恶性疟原虫环子孢子蛋白 (CSP) 的抗体，并且接种疫苗后针对 CSP 重复区域的免疫球蛋白 G (IgG) 浓度与预防恶性疟原虫疟疾相关。到目前为止，仅测量了抗 CSP IgG 的数量并用于预测疫苗接种的成功，尽管抗原-抗体相互作用的质量（以亲和力测量）很重要，因为在传染性蚊子叮咬后只有少数子孢子在短时间内循环，可能需要快速和强的结合。方法：在 0-1-2 个月或 1 个月内接受 RTS,S/AS01(E) 的非洲婴儿中抗 CSP IgG 的数量和亲和力通过酶联免疫吸附测定对 0 1 7 个月的 2 期临床试验进行了测定。抗体亲和力定义为在离液剂存在的情况下能够结合的 IgG 比例（亲和力指数）。使用 Cox 比例风险对 CSP 特异性 IgG 浓度和亲和力对保护功效的影响进行建模。结果：第三次接种后，两种疫苗接种方案之间的数量和亲合力相似。最后一次疫苗注射后的 IgG 亲和力与保护作用无关，而在亲和力变化高于中位数的参与者中，第二次和第三次 RTS,S/AS01(E) 注射后亲和力的变化与感染疟疾的风险降低 54% 相关（风险比：0.46；95% 置信区间 (CI)：0.22-0.99）。第二次和第三次注射后抗 CSP IgG 浓度的变化与疟疾风险降低 77% 相关（风险比：0.23，95% CI：0.11-0.51）。结论：疫苗剂量之间 IgG 反应的变化值得进一步评估，作为 RTS,S 功效的替代标志物。
Background: The malaria vaccine RTS,S induces antibodies against the Plasmodium falciparum circumsporozoite protein (CSP) and the concentration of Immunoglobulin G (IgG) against the repeat region of CSP following vaccination is associated with protection from P. falciparum malaria. So far, only the quantity of anti-CSP IgG has been measured and used to predict vaccination success, although quality (measured as avidity) of the antigen-antibody interaction shall be important since only a few sporozoites circulate for a short time after an infectious mosquito bite, likely requiring fast and strong binding.Methods: Quantity and avidity of anti-CSP IgG in African infants who received RTS,S/AS01(E) in a 0-1-2-month or a 0 1 7 month schedule in a phase 2 clinical trial were measured by enzyme-linked immunosorbent assay. Antibody avidity was defined as the proportion of IgG able to bind in the presence of a chaotropic agent (avidity index). The effect of CSP-specific IgG concentration and avidity on protective efficacy was modelled using Cox proportional hazards.Results: After the third dose, quantity and avidity were similar between the two vaccination schedules. IgG avidity after the last vaccine injection was not associated with protection, whereas the change in avidity following second and third RTS,S/AS01(E) injection was associated with a 54% risk reduction of getting malaria (hazard ratio: 0.46; 95% confidence interval (CI): 0.22-0.99) in those participants with a change in avidity above the median. The change in anti-CSP IgG concentration following second and third injection was associated with a 77% risk reduction of getting malaria (hazard ratio: 0.23, 95% CI: 0.11-0.51).Conclusions: Change in IgG response between vaccine doses merits further evaluation as a surrogate marker for RTS,S efficacy.