Human vaccination against Plasmodium vivax Duffy-binding protein induces strain-transcending antibodies
Human vaccination against Plasmodium vivax Duffy-binding protein induces strain-transcending antibodies
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DOI：
10.1172/jci.insight.96381
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发表时间：
2017-06-15
期刊：
影响因子：
8
通讯作者：
Draper, Simon J.
中科院分区：
文献类型：
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作者：
Payne, Ruth O.;Silk, Sarah E.;Draper, Simon J.
背景间日疟原虫是地理上分布最广的人类疟疾;然而，没有有效的疫苗存在。间日疟原虫裂殖子侵入红细胞依赖于趋化因子的达菲抗原受体（DARC）和寄生虫达菲结合蛋白（PvDBP_RII）的II区之间的相互作用。针对这种相互作用的自然获得的结合抑制抗体与临床免疫相关，但这些反应是否可以通过人类疫苗接种诱导尚不清楚。在一项开放标签剂量递增Ia期研究中，在24名健康英国成年人中评估了靶向PvDBP_RII（萨尔瓦多I株）的复制缺陷型黑猩猩腺病毒血清型63（ChAd 63）和改良的安卡拉牛痘病毒（MVA）病毒载体疫苗的安全性和免疫原性。使用8周的间隔，以ChAd 63-MVA异源初免-加强方案通过肌内途径递送疫苗。两种疫苗均具有良好的耐受性，并在未患疟疾的成人中表现出良好的安全性。在MVA加强免疫后观察PvDBP_RII特异性离体IFN-γ T细胞、抗体分泌细胞、记忆B细胞和血清IgG应答。疫苗诱导的抗体可抑制重组PvDBP_RII疫苗同源和异源变体与DARC受体的结合，半数结合抑制滴度大于1：100。据我们所知，我们首次证明了通过在人体中接种疫苗可以诱导针对PvDBP_RII抗原的跨菌株抗体。这些候选疫苗保证了对血液阶段间日疟原虫的有效性的进一步临床评价。
BACKGROUND. Plasmodium vivax is the most widespread human malaria geographically; however, no effective vaccine exists. Red blood cell invasion by the P. vivax merozoite depends on an interaction between the Duffy antigen receptor for chemokines (DARC) and region II of the parasite's Duffy-binding protein (PvDBP_RII). Naturally acquired binding-inhibitory antibodies against this interaction associate with clinical immunity, but it is unknown whether these responses can be induced by human vaccination.METHODS. Safety and immunogenicity of replication-deficient chimpanzee adenovirus serotype 63 (ChAd63) and modified vaccinia virus Ankara (MVA) viral vectored vaccines targeting PvDBP_RII (Salvador I strain) were assessed in an open-label dose-escalation phase Ia study in 24 healthy UK adults. Vaccines were delivered by the intramuscular route in a ChAd63-MVA heterologous prime-boost regimen using an 8-week interval.RESULTS. Both vaccines were well tolerated and demonstrated a favorable safety profile in malaria-naive adults. PvDBP_RII-specific ex-vivo IFN-gamma T cell, antibody-secreting cell, memory B cell, and serum IgG responses were observed after the MVA boost immunization. Vaccine-induced antibodies inhibited the binding of vaccine homologous and heterologous variants of recombinant PvDBP_RII to the DARC receptor, with median 50% binding-inhibition titers greater than 1:100.CONCLUSION. We have demonstrated for the first time to our knowledge that strain-transcending antibodies can be induced against the PvDBP_RII antigen by vaccination in humans. These vaccine candidates warrant further clinical evaluation of efficacy against the blood-stage P. vivax parasite.