Cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised placebo-controlled trial.
Cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant in transplant recipients: a phase 2 randomised placebo-controlled trial.
复制标题
DOI：
10.1016/s0140-6736(11)60136-0
复制
发表时间：
2011-04-09
期刊：
影响因子：
168.9
通讯作者：
Burroughs, Andrew K.
中科院分区：
文献类型：
--
作者：
Griffiths, Paul D.;Stanton, Anna;McCarrell, Erin;Smith, Colette;Osman, Mohamed;Harber, Mark;Davenport, Andrew;Jones, Gareth;Wheeler, David C.;O'Beirne, James;Thorburn, Douglas;Patch, David;Atkinson, Claire E.;Pichon, Sylvie;Sweny, Paul;Lanzman, Marisa;Woodford, Elizabeth;Rothwell, Emily;Old, Natasha;Kinyanjui, Ruth;Haque, Tanzina;Atabani, Sowsan;Luck, Suzanne;Prideaux, Steven;Milne, Richard S. B.;Emery, Vincent C.;Burroughs, Andrew K.
在同种异体移植受者中检测到病毒血症时，给予更昔洛韦可以预防巨细胞病毒终末器官疾病。病毒载量的值与终末器官疾病的发展相关，并受到先前存在的自然免疫的调节。我们的目标是确定疫苗诱导的免疫是否也能起到同样的作用。我们在英国伦敦皇家自由医院对等待肾或肝移植的成年人进行了2期随机安慰剂对照试验。排除标准为怀孕、在过去3个月内接受血液制品(白蛋白除外)以及同时进行多器官移植。70例巨细胞病毒血清阴性和70例巨细胞病毒血清阳性患者按1：1比例从刮除随机代码中随机分配，接受含有MF59佐剂的巨细胞病毒糖蛋白B疫苗或安慰剂，分别在基线、1个月和6个月后给予。如果患者被移植，则不再给予进一步的疫苗接种，并通过实时定量聚合酶链式反应(RtqPCR)对系列血样进行巨细胞病毒DNA检测。任何一个血液样本每毫升含有3000个以上巨细胞病毒基因组的患者都接受更昔洛韦治疗，直到连续两次无法检测到巨细胞病毒DNA为止。安全性和免疫原性是共同的终点，并根据接受至少一剂疫苗或安慰剂的患者的治疗意图进行评估。这项试验在ClinicalTrials.gov注册，NCT00299260。67名患者接受了疫苗接种，73名患者接受了安慰剂治疗，所有患者都可以进行评估。血清阴性(几何平均滴度12 537(95%CI6593-23 840)对86(63-118))和血清阳性(118 395； 503-217 272)的糖蛋白B抗体滴度在接种疫苗的24例 682(17 909-34 017)中显著升高(P<；0·0001)。在移植后出现病毒血症的患者中，糖蛋白B抗体滴度与病毒血症持续时间呈负相关(p=0.0022)。在血清阴性献血者中，接受疫苗接种的患者病毒血症持续时间(p=0.0480)和更昔洛韦治疗天数(p=0.0287)均缩短。虽然巨细胞病毒病是在移植后细胞免疫抑制的情况下发生的，但体液免疫在减少巨细胞病毒血症方面具有一定的作用。含有巨细胞病毒糖蛋白B的疫苗值得在移植受者中进一步评估。，Grant R01AI051355和Grant 078332。赞助商：伦敦大学学院(UCL)。
Cytomegalovirus end-organ disease can be prevented by giving ganciclovir when viraemia is detected in allograft recipients. Values of viral load correlate with development of end-organ disease and are moderated by pre-existing natural immunity. Our aim was to determine whether vaccine-induced immunity could do likewise. We undertook a phase-2 randomised placebo controlled trial in adults awaiting kidney or liver transplantation at the Royal Free Hospital, London, UK. Exclusion criteria were pregnancy, receipt of blood products (except albumin) in the previous 3 months, and simultaneous multiorgan transplantation. 70 patients seronegative and 70 seropositive for cytomegalovirus were randomly assigned from a scratch-off randomisation code in a 1:1 ratio to receive either cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant or placebo, each given at baseline, 1 month and 6 months later. If a patient was transplanted, no further vaccinations were given and serial blood samples were tested for cytomegalovirus DNA by real-time quantitative PCR (rtqPCR). Any patient with one blood sample containing more than 3000 cytomegalovirus genomes per mL received ganciclovir until two consecutive undetectable cytomegalovirus DNA measurements. Safety and immunogenicity were coprimary endpoints and were assessed by intention to treat in patients who received at least one dose of vaccine or placebo. This trial is registered with ClinicalTrials.gov, NCT00299260. 67 patients received vaccine and 73 placebo, all of whom were evaluable. Glycoprotein-B antibody titres were significantly increased in both seronegative (geometric mean titre 12 537 (95% CI 6593–23 840) versus 86 (63–118) in recipients of placebo recipients; p<0·0001) and seropositive (118 395; 64 503–217 272) versus 24 682 (17 909–34 017); p<0·0001) recipients of vaccine. In those who developed viraemia after transplantation, glycoprotein-B antibody titres correlated inversely with duration of viraemia (p=0·0022). In the seronegative patients with seropositive donors, the duration of viraemia (p=0·0480) and number of days of ganciclovir treatment (p=0·0287) were reduced in vaccine recipients. Although cytomegalovirus disease occurs in the context of suppressed cell-mediated immunity post-transplantation, humoral immunity has a role in reduction of cytomegalovirus viraemia. Vaccines containing cytomegalovirus glycoprotein B merit further assessment in transplant recipients. , Grant R01AI051355 and , Grant 078332. Sponsor: University College London (UCL).