Seronegative patients vaccinated with cytomegalovirus gB-MF59 vaccine have evidence of neutralising antibody responses against gB early post-transplantation
Seronegative patients vaccinated with cytomegalovirus gB-MF59 vaccine have evidence of neutralising antibody responses against gB early post-transplantation
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DOI：
10.1016/j.ebiom.2019.11.005
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发表时间：
2019-12-01
期刊：
影响因子：
11.1
通讯作者：
Reeves, Matthew B.
中科院分区：
文献类型：
--
作者：
Baraniak, Ilona;Gomes, Ariane C.;Reeves, Matthew B.
背景：人类巨细胞病毒(HCMV)可引起一种普遍的感染，对免疫功能低下的人，如实体器官移植(SOT)患者，可构成重大威胁。可以说，迄今为止研究最成功的疫苗是含有MF59佐剂的重组糖蛋白-B(GB)，在3个II期试验中，该疫苗在预防血清阴性的健康妇女或青少年感染HCMV以及SOT后病毒学参数下降方面显示出43-50%的有效性。然而，疫苗对血清阴性受者的保护机制仍不明确。方法：我们评估了参加第二阶段糖蛋白B/MF59疫苗试验的血清阴性SOT患者的样本，这些患者接受了血清阳性捐赠者的器官。SOT后(0~90d)标本用实时荧光定量聚合酶链式反应检测HCMV DNA。用双抗体夹心法检测血清抗GB抗体水平。中和是通过表达即刻早期抗原来衡量对成纤维细胞培养的感染力的降低。结果：血清学分析显示，疫苗接受者移植后对GB的体液反应比随机接受安慰剂的人增加得更快。重要的是，一些患者血清显示出HCMV中和反应，这种中和反应通过用重组gB预先吸收血清而被取消。解释：我们假设疫苗启动了血清阴性接受者的免疫系统，当移植时进一步受到病毒攻击时，允许宿主即使在移植期间T细胞免疫抑制的情况下也能产生快速的免疫体液反应。(C)2019年提交人。爱思唯尔出版公司(Elsevier B.V.)
Background: Human cytomegalovirus (HCMV) causes a ubiquitous infection which can pose a significant threat for immunocompromised individuals, such as those undergoing solid organ transplant (SOT). Arguably, the most successful vaccine studied to date is the recombinant glycoprotein-B (gB) with MF59 adjuvant which, in 3 Phase II trials, demonstrated 43-50% efficacy in preventing HCMV acquisition in seronegative healthy women or adolescents and reduction in virological parameters after SOT. However, the mechanism of vaccine protection in seronegative recipients remains undefined.Methods: We evaluated samples from the cohort of seronegative SOT patients enroled in the Phase II glycoprotein-B/MF59 vaccine trial who received organs from seropositive donors. Samples after SOT (0-90 days) were tested by real-time quantitative PCR for HCMV DNA. Anti-gB antibody levels were measured by ELISA. Neutralization was measured as a decrease in infectivity for fibroblast cell cultures revealed by expression of immediate-early antigens.Findings: Serological analyses revealed a more rapid increase in the humoral response against gB post transplant in vaccine recipients than in those randomised to receive placebo. Importantly, a number of patient sera displayed HCMV neutralising responses neutralisation which was abrogated by pre-absorbing the sera with recombinant gB.Interpretation: We hypothesise that the vaccine primed the immune system of seronegative recipients which, when further challenged with virus at time of transplant, allowed the host to mount rapid immunological humoral responses even under conditions of T cell immune suppression during transplantation. (C) 2019 The Authors. Published by Elsevier B.V.