Institute for Glycomics, Griffith University, Parklands Drive, Southport, Queensland, Australia.
Gold Coast University Hospital, 1 Hospital Blvd, Southport, Queensland, Australia.
BMC Med. 2018 Oct 8;16(1):184. doi: 10.1186/s12916-018-1173-9.
The continuing morbidity and mortality associated with infection with malaria parasites highlights the urgent need for a vaccine. The efficacy of sub-unit vaccines tested in clinical trials in malaria-endemic areas has thus far been disappointing, sparking renewed interest in the whole parasite vaccine approach. We previously showed that a chemically attenuated whole parasite asexual blood-stage vaccine induced CD4 T cell-dependent protection against challenge with homologous and heterologous parasites in rodent models of malaria.
In this current study, we evaluated the immunogenicity and safety of chemically attenuated asexual blood-stage Plasmodium falciparum (Pf) parasites in eight malaria-naïve human volunteers. Study participants received a single dose of 3 × 10 Pf pRBC that had been treated in vitro with the cyclopropylpyrolloindole analogue, tafuramycin-A.
We demonstrate that Pf asexual blood-stage parasites that are completely attenuated are immunogenic, safe and well tolerated in malaria-naïve volunteers. Following vaccination with a single dose, species and strain transcending Plasmodium-specific T cell responses were induced in recipients. This included induction of Plasmodium-specific lymphoproliferative responses, T cells secreting the parasiticidal cytokines, IFN-γ and TNF, and CD3CD45RO memory T cells. Pf-specific IgG was not detected.
This is the first clinical study evaluating a whole parasite blood-stage malaria vaccine. Following administration of a single dose of completely attenuated Pf asexual blood-stage parasites, Plasmodium-specific T cell responses were induced while Pf-specific antibodies were not detected. These results support further evaluation of this chemically attenuated vaccine in humans.
Trial registration: ACTRN12614000228684 . Registered 4 March 2014.
疟疾寄生虫感染相关的持续发病率和死亡率突出表明迫切需要疫苗。迄今为止，在疟疾流行地区进行临床试验的亚单位疫苗的疗效令人失望，这激发了人们对整个寄生虫疫苗方法的重新关注。我们之前表明，化学减毒的整个寄生虫无性血阶段疫苗在疟疾啮齿动物模型中诱导了 CD4 T 细胞依赖性保护，以抵抗同源和异源寄生虫的挑战。
在这项当前的研究中，我们评估了化学减毒的恶性疟原虫（Pf）无性血阶段寄生虫在 8 名疟疾-naïve 人类志愿者中的免疫原性和安全性。研究参与者接受了 3×10 Pf pRBC 的单次剂量，该剂量已在体外用环丙基吡咯烷吲哚类似物，tafura 霉素-A 处理。
我们证明完全减毒的 Pf 无性血阶段寄生虫是免疫原性的，在疟疾-naïve 志愿者中安全且耐受良好。接种一剂后，受者中诱导了跨物种和株的疟原虫特异性 T 细胞反应。这包括诱导疟原虫特异性淋巴增生反应，分泌细胞毒性细胞因子 IFN-γ和 TNF 的 T 细胞，以及 CD3CD45RO 记忆 T 细胞。未检测到 Pf 特异性 IgG。
这是评估整个寄生虫血阶段疟疾疫苗的首次临床研究。在给予完全减毒的 Pf 无性血阶段寄生虫的一剂后，诱导了疟原虫特异性 T 细胞反应，而未检测到 Pf 特异性抗体。这些结果支持进一步在人类中评估这种化学减毒疫苗。
试验注册：ACTRN12614000228684。注册于 2014 年 3 月 4 日。
