Vaccine candidate discovery for the next generation of malaria vaccines.
Vaccine candidate discovery for the next generation of malaria vaccines.
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DOI：
10.1111/imm.12780
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发表时间：
2017-10
期刊：
影响因子：
6.4
通讯作者：
Osier FHA
中科院分区：
文献类型：
--
作者：
Tuju J;Kamuyu G;Murungi LM;Osier FHA
虽然流行病学观察、免疫球蛋白被动转移研究和人类实验性感染都支持开发高效疟疾疫苗的可行性，但诱导保护性免疫的确切抗原仍然不确定。在这里，我们回顾了从前基因组时代到后基因组时代应用于恶性疟疾疫苗候选发现的方法学。前者主要是用具有明确特异性或功能活性的抗体探测基因组和cDNA文库，而后者的主要支柱是反向疫苗学，包括对基因组、转录组或蛋白质组寄生虫数据集的高通量电子分析。抗体引导的疫苗设计跨越了两个时代，但目前受益于促进高通量筛选和下游应用的技术进步。我们认为，尽管我们在相对较短的时间内识别众多潜在候选疫苗的能力呈指数级增长，但在临床试验中对它们的验证和评估的优先顺序仍然是一个重大的瓶颈。纵向队列研究提供了支持性证据，但研究之间的结果往往相互矛盾。抗原特异性抗体功能的证明是有价值的，但一种机制相对于另一种机制在保护方面的相对重要性仍未确定。动物模型提供了有用的见解，但可能不能准确反映人类疾病。在人类身上进行挑战研究是可取的，但费用高得令人望而却步。在缺乏可靠的保护相关性、合适的动物模型或更好地了解人类保护性免疫的潜在机制的情况下，疫苗候选发现本身可能不足以提供开发下一代高效亚单位疟疾疫苗所需的范式转变。
Although epidemiological observations, IgG passive transfer studies and experimental infections in humans all support the feasibility of developing highly effective malaria vaccines, the precise antigens that induce protective immunity remain uncertain. Here, we review the methodologies applied to vaccine candidate discovery for Plasmodium falciparum malaria from the pre‐ to post‐genomic era. Probing of genomic and cDNA libraries with antibodies of defined specificities or functional activity predominated the former, whereas reverse vaccinology encompassing high throughput in silico analyses of genomic, transcriptomic or proteomic parasite data sets is the mainstay of the latter. Antibody‐guided vaccine design spanned both eras but currently benefits from technological advances facilitating high‐throughput screening and downstream applications. We make the case that although we have exponentially increased our ability to identify numerous potential vaccine candidates in a relatively short space of time, a significant bottleneck remains in their validation and prioritization for evaluation in clinical trials. Longitudinal cohort studies provide supportive evidence but results are often conflicting between studies. Demonstration of antigen‐specific antibody function is valuable but the relative importance of one mechanism over another with regards to protection remains undetermined. Animal models offer useful insights but may not accurately reflect human disease. Challenge studies in humans are preferable but prohibitively expensive. In the absence of reliable correlates of protection, suitable animal models or a better understanding of the mechanisms underlying protective immunity in humans, vaccine candidate discovery per se may not be sufficient to provide the paradigm shift necessary to develop the next generation of highly effective subunit malaria vaccines.
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
9.8
作者：
Bozdech, Zbynek;Llinas, Manuel;Pulliam, Brian Lee;Wong, Edith D;Zhu, Jingchun;DeRisi, Joseph L
通讯作者：
DeRisi, Joseph L
DOI：
10.1073/pnas.79.18.5651
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
COCHRANE, AH;SANTORO, F;NUSSENZWEIG, RS
通讯作者：
NUSSENZWEIG, RS
DOI：
10.1016/s0169-4758(96)10077-6
发表时间：
1997-01-01
期刊：
PARASITOLOGY TODAY
影响因子：
--
作者：
Conway, DJ
通讯作者：
Conway, DJ
DOI：
10.1073/pnas.90.17.8292
发表时间：
1993-09-01
影响因子：
11.1
作者：
DAY, KP;KARAMALIS, F;KEMP, DJ
通讯作者：
KEMP, DJ