Polymorphisms in key innate immune genes and their effects on measles vaccine responses and vaccine failure in children from Mozambique
Polymorphisms in key innate immune genes and their effects on measles vaccine responses and vaccine failure in children from Mozambique
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DOI：
10.1016/j.vaccine.2012.07.063
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发表时间：
2012-09-21
期刊：
影响因子：
5.5
通讯作者：
Le Souef, Peter N.
中科院分区：
文献类型：
--
作者：
Clifford, Holly D.;Hayden, Catherine M.;Le Souef, Peter N.
尽管有有效的疫苗，麻疹仍然是全球主要的健康问题，特别是在发展中国家。超过 30% 的儿童初次接种疫苗失败，因此仍然容易感染麻疹。关键先天病原体识别受体（例如麻疹细胞进入受体 CD46 和 SLAM、麻疹附着受体 DC-SIGN、抗病毒 Toll 样受体 (TLR)3、TLR7 和 TLR8 以及胞质抗病毒受体 RIG-I）的遗传变异可能会显着影响麻疹 IgG 抗体反应。麻疹在非洲等发展中国家仍然非常流行，但之前没有关于这些先天免疫基因对非洲居民的影响的数据。对来自非洲莫桑比克、年龄为 6 个月至 14 岁的一组接种疫苗的儿童 (n = 238) 进行了候选基因多态性 (n = 29) 的基因分型，这些儿童要么疫苗失败并感染麻疹（病例；n = 66），要么对照（n = 172）。对比之前与白种人麻疹反应的关联和/或候选资格的有力证据，我们发现几乎没有迹象表明这些关键的先天免疫基因会影响莫桑比克儿童群体中的麻疹 IgG 反应。然而，我们确实发现 CD46 和 TLR8 变异可能与麻疹疫苗失败的发生有关。这项研究强调了对居民、非白种人群体进行遗传学研究的重要性，这些地区优先考虑确定可能影响麻疹控制的因素。 (c) 2012 Elsevier Ltd. 保留所有权利。
Despite an effective vaccine, measles remains a major health problem globally, particularly in developing countries. More than 30% of children show primary vaccine failure and therefore remain vulnerable to measles. Genetic variation in key innate pathogen recognition receptors, such as the measles cell entry receptors CD46 and SLAM, measles attachment receptor DC-SIGN, the antiviral toll-like receptors (TLR)3, TLR7 and TLR8, and the cytosolic antiviral receptor RIG-I, may significantly affect measles IgG antibody responses. Measles is still highly prevalent in developing countries such as those in Africa however there is no previous data on the effect of these innate immune genes in a resident African population. Polymorphisms (n = 29) in the candidate genes were genotyped in a cohort of vaccinated children (n = 238) aged 6 months-14 years from Mozambique, Africa who either had vaccine failure and contracted measles (cases; n = 66) or controls (n = 172). Contrasting previous associations with measles responses in Caucasians and/or strong evidence for candidacy, we found little indication that these key innate immune genes affect measles IgG responses in our cohort of Mozambican children. We did however identify that CD46 and TLR8 variants may be involved in the occurrence of measles vaccine failure. This study highlights the importance of genetic studies in resident, non-Caucasian populations, from areas where determining the factors that may affect measles control is of a high priority. (c) 2012 Elsevier Ltd. All rights reserved.