Mensah Victorine A, Roetynck Sophie, Kanteh Ebrima K, Bowyer Georgina, Ndaw Amy, Oko Francis, Bliss Carly M, Jagne Ya Jankey, Cortese Riccardo, Nicosia Alfredo, Roberts Rachel, D'Alessio Flavia, Leroy Odile, Faye Babacar, Kampmann Beate, Cisse Badara, Bojang Kalifa, Gerry Stephen, Viebig Nicola K, Lawrie Alison M, Clarke Ed, Imoukhuede Egeruan B, Ewer Katie J, Hill Adrian V S, Afolabi Muhammed O
Université Cheikh Anta Diop, Dakar, Senegal.
Medical Research Council Unit, Fajara, Gambia.
Front Immunol. 2017 Nov 20;8:1551. doi: 10.3389/fimmu.2017.01551. eCollection 2017.
Heterologous prime-boost vaccination with chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) encoding multiple epitope string thrombospondin-related adhesion protein (ME-TRAP) has shown acceptable safety and promising immunogenicity in African adult and pediatric populations. If licensed, this vaccine could be given to infants receiving routine childhood immunizations. We therefore evaluated responses to ChAd63 MVA ME-TRAP when co-administered with routine Expanded Program on Immunization (EPI) vaccines.
We enrolled 65 Gambian infants and neonates, aged 16, 8, or 1 week at first vaccination and randomized them to receive either ME-TRAP and EPI vaccines or EPI vaccines only. Safety was assessed by the description of vaccine-related adverse events (AEs). Immunogenicity was evaluated using IFNγ enzyme-linked immunospot, whole-blood flow cytometry, and anti-TRAP IgG ELISA. Serology was performed to confirm all infants achieved protective titers to EPI vaccines.
The vaccines were well tolerated in all age groups with no vaccine-related serious AEs. High-level TRAP-specific IgG and T cell responses were generated after boosting with MVA. CD8 T cell responses, previously found to correlate with protection, were induced in all groups. Antibody responses to EPI vaccines were not altered significantly.
Malaria vectored prime-boost vaccines co-administered with routine childhood immunizations were well tolerated. Potent humoral and cellular immunity induced by ChAd63 MVA ME-TRAP did not reduce the immunogenicity of co-administered EPI vaccines, supporting further evaluation of this regimen in infant populations.
The clinical trial was registered on http://Clinicaltrials.gov (NCT02083887) and the Pan-African Clinical Trials Registry (PACTR201402000749217).
用编码多表位串联血小板反应蛋白相关粘附蛋白（ME-TRAP）的黑猩猩腺病毒63型（ChAd63）和安卡拉痘苗病毒（MVA）进行异源初免-加强免疫接种，已在非洲成人和儿童人群中显示出可接受的安全性和有前景的免疫原性。如果获得许可，这种疫苗可用于接受常规儿童免疫接种的婴儿。因此，我们评估了ChAd63 MVA ME-TRAP与常规扩大免疫规划（EPI）疫苗同时接种时的反应。
我们招募了65名冈比亚婴儿和新生儿，首次接种时年龄分别为16周、8周或1周，并将他们随机分为接受ME-TRAP和EPI疫苗组或仅接受EPI疫苗组。通过描述疫苗相关不良事件（AE）来评估安全性。使用IFNγ酶联免疫斑点法、全血流式细胞术和抗TRAP IgG ELISA评估免疫原性。进行血清学检测以确认所有婴儿对EPI疫苗达到保护性滴度。
所有年龄组对疫苗的耐受性良好，没有与疫苗相关的严重不良事件。用MVA加强免疫后产生了高水平的TRAP特异性IgG和T细胞反应。所有组均诱导出先前发现与保护相关的CD8 T细胞反应。对EPI疫苗的抗体反应没有显著改变。
与常规儿童免疫接种同时接种的疟疾载体初免-加强疫苗耐受性良好。ChAd63 MVA ME-TRAP诱导的强大体液和细胞免疫并未降低同时接种的EPI疫苗的免疫原性，支持在婴儿人群中进一步评估该方案。
该临床试验在http://Clinicaltrials.gov（NCT02083887）和泛非临床试验注册中心（PACTR201402000749217）注册。
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