The march toward malaria vaccines.
The march toward malaria vaccines.
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DOI：
10.1016/j.vaccine.2015.07.091
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发表时间：
2015-11-27
期刊：
影响因子：
5.5
通讯作者：
Duffy PE
中科院分区：
文献类型：
--
作者：
Hoffman SL;Vekemans J;Richie TL;Duffy PE
2013年，估计有584 000人死于疟疾，1.98亿人因疟疾临床患病，其中大部分在撒哈拉以南非洲。疫苗将是对现有抗疟疾工具的理想补充。然而，疟疾是由寄生虫引起的，寄生虫在生物学方面比我们有疫苗的病毒和细菌复杂得多，在人类宿主中经历多个发育阶段，每个阶段表达数百种独特的抗原。这种复杂性使得开发针对寄生虫的疫苗比针对病毒和细菌的疫苗更困难，因为针对一个阶段的免疫应答可能无法提供针对后期阶段的保护，因为不同的抗原是不同阶段的保护性免疫的目标。此外，根据生命周期阶段以及寄生虫是细胞外还是细胞内，抗体和/或细胞免疫应答提供保护。因此，市场上没有预防疟疾或任何人类寄生虫感染的疫苗也就不足为奇了。事实上，没有针对任何疾病的疫苗具有如此广泛的靶点和免疫反应。在这篇有限的综述中，我们集中在四种疟疾疫苗的方法，（1）针对恶性疟原虫（Pf）红细胞期前阶段的重组蛋白佐剂疫苗（RTS，S/AS 01），（2）针对Pf红细胞前期的全子孢子疫苗（PfSPZ疫苗和PfSPZ-CVac），（3）初免加强疫苗，其包括重组DNA、病毒和细菌，以及具有佐剂的蛋白质，主要针对Pf红细胞前，而且还包括无性红细胞期;（4）针对Pf和间日疟原虫有性红细胞期和蚊期的重组蛋白与佐剂疫苗。我们认识到，我们没有涵盖疟疾疫苗开发的所有方法，也没有涵盖针对间日疟原虫（疟疾的第二大最重要原因）的疫苗开发的大多数至关重要的工作。过去几年取得了重大进展，欧洲药品管理局（EMA）正在根据第58条审查第一代疟疾候选疫苗RTS，S/AS 01的质量，安全性和有效性，该条款允许EMA对专门用于欧盟以外市场的产品提出科学意见。然而，在保护效力的规模和持久性以及提供的资金和实用性方面，正在开展大量工作，以优化疟疾疫苗。因此，我们希望，抗疟疾疫苗不久将成为防治疟疾的重要工具。
In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of malaria. Progress during the last few years has been significant, and a first generation malaria candidate vaccine, RTS,S/AS01, is under review by the European Medicines Agency (EMA) for its quality, safety and efficacy under article 58, which allows the EMA to give a scientific opinion about products intended exclusively for markets outside of the European Union. However, much work is in progress to optimize malaria vaccines in regard to magnitude and durability of protective efficacy and the financing and practicality of delivery. Thus, we are hopeful that anti-malaria vaccines will soon be important tools in the battle against malaria.
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DOI：
10.1073/pnas.1220360110
发表时间：
2013-05-07
影响因子：
11.1
作者：
Bijker, Else M.;Bastiaens, Guido J. H.;Sauerwein, Robert W.
通讯作者：
Sauerwein, Robert W.
影响因子：
15.8
作者：
malERA Consultative Group on Vaccines
通讯作者：
malERA Consultative Group on Vaccines
影响因子：
10.5
作者：
Aly AS;Vaughan AM;Kappe SH
通讯作者：
Kappe SH
DOI：
10.1084/jem.20101488
发表时间：
2011-02-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Coppi A;Natarajan R;Pradel G;Bennett BL;James ER;Roggero MA;Corradin G;Persson C;Tewari R;Sinnis P
通讯作者：
Sinnis P
影响因子：
5.5
作者：
Blagborough, Andrew M.;Yoshida, Shigeto;Sinden, Robert E.
通讯作者：
Sinden, Robert E.