A malaria vaccine that elicits in humans antibodies able to kill Plasmodium falciparum.
A malaria vaccine that elicits in humans antibodies able to kill Plasmodium falciparum.
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DOI：
10.1371/journal.pmed.0020344
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发表时间：
2005-11
期刊：
影响因子：
15.8
通讯作者：
Roussilhon C
中科院分区：
文献类型：
--
作者：
Druilhe P;Spertini F;Soesoe D;Corradin G;Mejia P;Singh S;Audran R;Bouzidi A;Oeuvray C;Roussilhon C
恶性疟原虫裂殖子表面蛋白3是一种疟疾候选疫苗，它是根据一种独特的免疫临床方法进行鉴定、表征和开发的。该疫苗构建物来自各种菌株之间完全保守的区域，并包含由人类抗体(来自疟疾免疫成人)靶向的B细胞表位，这些抗体能够介导依赖单核细胞的寄生虫杀伤效应。36名志愿者被给予相应的长合成多肽，明矾或蒙丹尼德ISA720作为佐剂。这两种制剂都能诱导细胞和体液免疫反应。对于明矾，这种反应持续了12个月。疫苗诱导的抗体主要是亲细胞性的，即能够与效应细胞合作。在体外，这些抗体以单核细胞依赖的方式诱导对恶性疟原虫红细胞生长的抑制，在大多数情况下与来自免疫的非洲成虫的天然抗体诱导的抑制作用相当或更强。将志愿者的血清体内转移到感染恶性疟原虫的人源化SCID小鼠体内，可显著降低或消除寄生虫血症。这些抑制作用与抗体与寄生虫天然蛋白的反应性有关，在60%的志愿者中可以看到，并在免疫后12个月保持在样本中。这是第一次通过体外和体内方法清楚地证明疫苗诱导的抗体具有抗寄生虫活性的疟疾疫苗临床试验。结果表明，针对完全保守的多肽可以诱导出持久的抗体，这也挑战了目前有关疟疾疫苗的概念，如不可避免的多态、低抗原性和免疫记忆诱导差。功能分析表明，以MSP3为基础的疫苗在人类志愿者中引起了强烈的免疫反应。
Plasmodium falciparum merozoite surface protein 3 is a malaria vaccine candidate that was identified, characterised, and developed based on a unique immuno-clinical approach. The vaccine construct was derived from regions fully conserved among various strains and containing B cell epitopes targeted by human antibodies (from malaria-immune adults) that are able to mediate a monocyte-dependent parasite killing effect. The corresponding long synthetic peptide was administered to 36 volunteers, with either alum or Montanide ISA720 as adjuvant. Both formulations induced cellular and humoral immune responses. With alum, the responses lasted up to 12 mo. The vaccine-induced antibodies were predominantly of cytophilic classes, i.e., able to cooperate with effector cells. In vitro, the antibodies induced an inhibition of the P. falciparum erythrocytic growth in a monocyte-dependent manner, which was in most instances as high as or greater than that induced by natural antibodies from immune African adults. In vivo transfer of the volunteers' sera into P. falciparum–infected humanized SCID mice profoundly reduced or abrogated parasitaemia. These inhibitory effects were related to the antibody reactivity with the parasite native protein, which was seen in 60% of the volunteers, and remained in samples taken 12 mo postimmunisation. This is the first malaria vaccine clinical trial to clearly demonstrate antiparasitic activity by vaccine-induced antibodies by both in vitro and in vivo methods. The results, showing the induction of long-lasting antibodies directed to a fully conserved polypeptide, also challenge current concepts about malaria vaccines, such as unavoidable polymorphism, low antigenicity, and poor induction of immune memory. Functional assays suggest that MSP3-based vaccine elicits strong immune response in human volunteers.
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DOI：
10.4269/ajtmh.1996.55.63
发表时间：
1996-07-01
影响因子：
3.3
作者：
Gordon, DM;Duffy, PE;Ballou, WR
通讯作者：
Ballou, WR
影响因子：
4.9
作者：
Moreno, A;Badell, E;Druilhe, P
通讯作者：
Druilhe, P
影响因子：
1.5
作者：
McColl, DJ;Anders, RF
通讯作者：
Anders, RF
影响因子：
3.6
作者：
Mills, KE;Pearce, JA;Cowman, AF
通讯作者：
Cowman, AF
影响因子：
15.3
作者：
BOUHAROUNTAYOUN, H;OEUVRAY, C;DRUILHE, P
通讯作者：
DRUILHE, P