Poxvirus Vectored Cytomegalovirus Vaccine to Prevent Cytomegalovirus Viremia in Transplant Recipients: A Phase 2, Randomized Clinical Trial.
Poxvirus Vectored Cytomegalovirus Vaccine to Prevent Cytomegalovirus Viremia in Transplant Recipients: A Phase 2, Randomized Clinical Trial.
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DOI：
10.7326/m19-2511
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发表时间：
2020-03-03
影响因子：
39.2
通讯作者：
Diamond, Don J.
中科院分区：
文献类型：
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作者：
Aldoss, Ibrahim;La Rosa, Corinna;Baden, Lindsey R.;Longmate, Jeffrey;Ariza-Heredia, Ella J.;Rida, Wasima N.;Lingaraju, Chetan Raj;Zhou, Qiao;Martinez, Joy;Kaltcheva, Teodora;Dagis, Andy;Hardwick, Nicola;Issa, Nicolas C.;Farol, Len;Nademanee, Auayporn;Al Malki, Monzr M.;Forman, Stephen;Nakamura, Ryotaro;Diamond, Don J.
开发了三联疫苗以在造血干细胞移植（HCT）后早期增强CMV特异性T细胞并防止CMV再活化。确定Triplex的安全性和有效性。首次入组患者II期试验（ClinicalTrials.gov：NCT 02506933）。三个美国HCT中心。102名CMV血清阳性HCT接受者，存在CMV再激活的高风险。HCT后第28天和第56天肌内注射Triplex或安慰剂。Triplex是一种重组减毒痘病毒，改良的安卡拉牛痘，表达免疫显性CMV抗原。主要结局为：CMV事件（≥1250 IU/mL;需要抗病毒药物的CMV病毒血症;或终末器官疾病）;非复发性死亡率;重度（3级、4级）GVHD，均评价至HCT后100天，以及接种后2周内的3-4级不良事件（AE，很可能或明确归因于注射）。102例患者接受了首次疫苗接种（51例/组），91例（89.2%）接受了两次疫苗接种（46例三联疫苗，45例安慰剂）。与10例安慰剂组（19.6%）相比，5例三联治疗组（9.8%）发生CMV再激活（风险比，0.46; 95%CI，0.16 - 1.4; P=0.075）。在接种后的前100天内，无三联疫苗接种者发生非复发性死亡或严重AE，接种后2周内未观察到与疫苗接种相关的3-4级AE。注射后，两组之间严重急性GVHD的发生率相似（风险比，1.1; 95%CI，0.53至2.4; P=0.23）。与安慰剂接受者相比，在Triplex中测量到显著更高水平的具有效应记忆表型的持久pp 65特异性T细胞。安慰剂组中CMV事件发生率低于预期降低了试验的把握度。未发现疫苗相关安全性问题。Triplex引起并增强了CMV特异性免疫应答，并且更少的Triplex疫苗接种患者经历CMV病毒血症。国家癌症研究所和Helocyte Inc.
Triplex vaccine was developed to enhance CMV specific T-cells and prevent CMV reactivation, early after hematopoietic stem cell transplantation (HCT). To determine safety and efficacy of Triplex. First-in-patient phase 2 trial (ClinicalTrials.gov: NCT02506933). Three U.S. HCT centers. 102 CMV-seropositive HCT recipients, at high-risk for CMV reactivation. Intramuscular injections on days 28 and 56 post-HCT of Triplex or placebo. Triplex is a recombinant attenuated poxvirus, modified vaccinia Ankara, expressing immunodominant CMV antigens. The primary outcomes were: CMV events (≥1250 IU/mL; CMV viremia requiring antivirals; or end-organ disease); non-relapse mortality; severe (grade 3, 4) GVHD, all evaluated through 100 days post-HCT, and grade 3-4 adverse events (AEs, probably or definitely attributable to injection) within 2 weeks post-vaccination. 102 patients received the first vaccination (51/group), 91 (89.2%) received both vaccinations (46 Triplex, 45 placebo). CMV reactivation occurred in 5 Triplex (9.8%), compared to 10 placebo (19.6%) recipients (hazard ratio, 0.46; 95% CI, 0.16 to 1.4; P=0.075). No Triplex recipient experienced non-relapse mortality during the first 100 days or serious AEs, no grade 3-4 AEs related to vaccination within 2 weeks post-vaccination was observed. Incidence of severe acute GVHD was similar between groups, post-injection (hazard ratio, 1.1; 95% CI, 0.53 to 2.4; P=0.23). Significantly higher levels of long lasting pp65-specific T-cells with effector memory phenotype were measured in Triplex compared to placebo recipients. The lower-than-expected CMV event incidence in the placebo group reduced the power of the trial. No vaccine associated safety concerns were identified. Triplex elicited and amplified CMV-specific immune responses, and fewer Triplex vaccinated patients experienced CMV viremia. National Cancer Institute and Helocyte Inc.