Epitope-Specific Humoral Responses to Human Cytomegalovirus Glycoprotein-B Vaccine With MF59: Anti-AD2 Levels Correlate With Protection From Viremia.
Epitope-Specific Humoral Responses to Human Cytomegalovirus Glycoprotein-B Vaccine With MF59: Anti-AD2 Levels Correlate With Protection From Viremia.
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DOI：
10.1093/infdis/jiy102
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发表时间：
2018-05-25
期刊：
影响因子：
--
通讯作者：
Reeves MB
中科院分区：
文献类型：
--
作者：
Baraniak I;Kropff B;McLean GR;Pichon S;Piras-Douce F;Milne RSB;Smith C;Mach M;Griffiths PD;Reeves MB
人巨细胞病毒（HCMV）糖蛋白B （gB）在体内产生巨大的多克隆抗体反应。抗体检测到抗原结构域2的患者在移植后表现出较低的病毒血症，在重组gB疫苗的接受者中，病毒血症水平得到提高。人巨细胞病毒（HCMV）病毒粒子包膜蛋白糖蛋白B （gB）对病毒进入至关重要，是感染后体液反应的主要靶点。此前，在实体器官移植候选人中进行的一项2期安慰剂对照临床试验表明，接种gB + MF59佐剂可显著提高gB酶联免疫吸附试验（ELISA）抗体水平，其滴度与对移植后病毒血症的保护直接相关。当前研究的目的是更详细地调查免疫血清阳性移植受者的保护性体液反应。我们重点研究了gB的4个关键抗原域（AD1、AD2、AD4和AD5），测量了患者血清中的抗体水平，并将其与移植后HCMV病毒血症联系起来。血清阳性患者接种疫苗可显著提高预先存在的针对免疫优势区AD1以及针对AD2、AD4和AD5的抗体水平。病毒血症发生率的降低与抗AD2抗体水平升高相关，但与抗其他3种ad抗体水平无关。总的来说，这些数据支持了一种假设，即抗AD2抗体是接种gB/MF59疫苗后血清阳性患者免疫保护的主要组成部分，并确定了同种异体移植患者保护性免疫的相关性。
Human cytomegalovirus (HCMV) glycoprotein B (gB) generates a prodigious polyclonal antibody response in vivo. Patients with antibodies that detect antigenic domain 2 display reduced viraemia post transplant - levels of which are boosted in recipients of a recombinant gB vaccine. The human cytomegalovirus (HCMV) virion envelope protein glycoprotein B (gB) is essential for viral entry and represents a major target for humoral responses following infection. Previously, a phase 2 placebo-controlled clinical trial conducted in solid organ transplant candidates demonstrated that vaccination with gB plus MF59 adjuvant significantly increased gB enzyme-linked immunosorbent assay (ELISA) antibody levels whose titer correlated directly with protection against posttransplant viremia. The aim of the current study was to investigate in more detail this protective humoral response in vaccinated seropositive transplant recipients. We focused on 4 key antigenic domains (AD) of gB (AD1, AD2, AD4, and AD5), measuring antibody levels in patient sera and correlating these with posttransplant HCMV viremia. Vaccination of seropositive patients significantly boosted preexisting antibody levels against the immunodominant region AD1 as well as against AD2, AD4, and AD5. A decreased incidence of viremia correlated with higher antibody levels against AD2 but not with antibody levels against the other 3 ADs. Overall, these data support the hypothesis that antibodies against AD2 are a major component of the immune protection of seropositives seen following vaccination with gB/MF59 vaccine and identify a correlate of protective immunity in allograft patients.
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影响因子：
5.5
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Bernstein DI;Munoz FM;Callahan ST;Rupp R;Wootton SH;Edwards KM;Turley CB;Stanberry LR;Patel SM;Mcneal MM;Pichon S;Amegashie C;Bellamy AR
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