Viral Vector Malaria Vaccines Induce High-Level T Cell and Antibody Responses in West African Children and Infants.
Viral Vector Malaria Vaccines Induce High-Level T Cell and Antibody Responses in West African Children and Infants.
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DOI：
10.1016/j.ymthe.2016.11.003
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发表时间：
2017-02-01
期刊：
影响因子：
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通讯作者：
Ewer KJ
中科院分区：
文献类型：
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作者：
Bliss CM;Drammeh A;Bowyer G;Sanou GS;Jagne YJ;Ouedraogo O;Edwards NJ;Tarama C;Ouedraogo N;Ouedraogo M;Njie-Jobe J;Diarra A;Afolabi MO;Tiono AB;Yaro JB;Adetifa UJ;Hodgson SH;Anagnostou NA;Roberts R;Duncan CJ;Cortese R;Viebig NK;Leroy O;Lawrie AM;Flanagan KL;Kampmann B;Imoukhuede EB;Sirima SB;Bojang K;Hill AV;Nébié I;Ewer KJ
用编码与多表位串融合的红细胞前抗原血小板反应蛋白相关粘附蛋白（ME-TRAP）的病毒载体进行的异源性初免加强免疫诱导了欧洲疟疾初治和肯尼亚半免疫成人对疟疾子孢子攻击的CD 8 + T细胞介导的免疫。这种方法尚未在儿童和婴儿中进行评估。我们在138名冈比亚和布基纳法索儿童中评估了这一疫苗策略，分为四个队列：冈比亚的2至6岁奥尔兹，布基纳法索的5至17个月大的儿童，冈比亚的5至12个月大和10周大的儿童。我们评估了细胞免疫的诱导，考虑到不同的血液学状态的幼儿，并表征了抗体反应的疫苗接种。T细胞应答在用改良的安卡拉牛痘病毒（MVA）加强后7天达到峰值，在引发时10周龄的婴儿中应答最高。将淋巴细胞计数纳入T细胞反应的计算中，有助于在不同年龄组之间进行更具生理相关性的细胞免疫比较。CD 8+和CD 4 + T细胞均分泌细胞因子。与冈比亚和英国（UK）成人相比，所有组中诱导的抗体高达20倍，具有相当或更高的亲和力。这种免疫方案引起了强烈的免疫应答，特别是在年幼的婴儿中，支持未来对疟疾疫苗在这一关键目标年龄组中的效力进行评价。有效的疟疾疫苗是全球卫生的一个紧迫优先事项。在这些研究中，Ewer及其同事描述了儿童和婴儿接种编码红细胞前疟疾抗原的病毒载体疫苗方案后的强烈T细胞和抗体应答。该方案先前已证明在成人中有效，这些数据支持评估该疫苗在婴儿中的有效性。
Heterologous prime-boosting with viral vectors encoding the pre-erythrocytic antigen thrombospondin-related adhesion protein fused to a multiple epitope string (ME-TRAP) induces CD8+ T cell-mediated immunity to malaria sporozoite challenge in European malaria-naive and Kenyan semi-immune adults. This approach has yet to be evaluated in children and infants. We assessed this vaccine strategy among 138 Gambian and Burkinabe children in four cohorts: 2- to 6-year olds in The Gambia, 5- to 17-month-olds in Burkina Faso, and 5- to 12-month-olds and 10-week-olds in The Gambia. We assessed induction of cellular immunity, taking into account the distinctive hematological status of young infants, and characterized the antibody response to vaccination. T cell responses peaked 7 days after boosting with modified vaccinia virus Ankara (MVA), with highest responses in infants aged 10 weeks at priming. Incorporating lymphocyte count into the calculation of T cell responses facilitated a more physiologically relevant comparison of cellular immunity across different age groups. Both CD8+ and CD4+ T cells secreted cytokines. Induced antibodies were up to 20-fold higher in all groups compared with Gambian and United Kingdom (UK) adults, with comparable or higher avidity. This immunization regimen elicited strong immune responses, particularly in young infants, supporting future evaluation of efficacy in this key target age group for a malaria vaccine. An effective malaria vaccine is an urgent global health priority. In these studies, Ewer and colleagues describe strong T cell and antibody responses in children and infants following vaccination with a viral vectored vaccine regime encoding a pre-erythrocytic malaria antigen. This regime has previously demonstrated efficacy in adults and these data support assessment of the efficacy of this vaccine in infants.