抗体针对不同环子孢子蛋白表位的浓度和亲和力与 RTS,S/AS01E 疟疾疫苗的功效相关。

Concentration and avidity of antibodies to different circumsporozoite epitopes correlate with RTS,S/AS01E malaria vaccine efficacy.

机构信息

ISGlobal, Hospital Clínic - Universitat de Barcelona, Rosselló 153, 08036, Barcelona, Catalonia, Spain.

Centro de Investigação em Saúde de Manhiça (CISM), Rua 12, Cambeve, Vila de Manhiça, CP 1929, Maputo, Mozambique.

出版信息

Nat Commun. 2019 May 15;10(1):2174. doi: 10.1038/s41467-019-10195-z.

DOI:10.1038/s41467-019-10195-z

PMID:31092823

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6520358/

Abstract

RTS,S/AS01E has been tested in a phase 3 malaria vaccine study with partial efficacy in African children and infants. In a cohort of 1028 subjects from one low (Bagomoyo) and two high (Nanoro, Kintampo) malaria transmission sites, we analysed IgG plasma/serum concentration and avidity to CSP (NANP-repeat and C-terminal domains) after a 3-dose vaccination against time to clinical malaria events during 12-months. Here we report that RTS,S/AS01E induces substantial increases in IgG levels from pre- to post-vaccination (p < 0.001), higher in NANP than C-terminus (2855 vs 1297 proportional change between means), and higher concentrations and avidities in children than infants (p < 0.001). Baseline CSP IgG levels are elevated in malaria cases than controls (p < 0.001). Both, IgG magnitude to NANP (hazard ratio [95% confidence interval] 0.61 [0.48-0.76]) and avidity to C-terminus (0.07 [0.05-0.90]) post-vaccination are significantly associated with vaccine efficacy. IgG avidity to the C-terminus emerges as a significant contributor to RTS,S/AS01E-mediated protection.

摘要

RTS,S/AS01E 在一项针对非洲儿童和婴儿的疟疾疫苗 III 期研究中进行了测试，结果显示其具有部分疗效。在一个来自低（Bagomoyo）、两个高（Nanoro、Kintampo）疟疾传播地区的 1028 名受试者队列中，我们分析了在 12 个月的时间内对 CSP（NANP 重复序列和 C 末端结构域）进行三剂接种后的 IgG 血浆/血清浓度和亲和力，以预防临床疟疾事件。在这里，我们报告 RTS,S/AS01E 诱导 IgG 水平从接种前到接种后显著增加（p<0.001），NANP 比 C 末端更高（均值之间的比例变化为 2855 比 1297），儿童比婴儿更高（p<0.001）。与对照组相比，疟疾病例的 CSP IgG 水平升高（p<0.001）。接种后 NANP 的 IgG 数量（危险比[95%置信区间]0.61[0.48-0.76]）和 C 末端的亲和力（0.07[0.05-0.90]）都与疫苗的疗效显著相关。C 末端的 IgG 亲和力是 RTS,S/AS01E 介导的保护作用的一个重要贡献因素。