Understanding Human-Derived Antibodies Generated by Polymorphic Malaria Vaccine Against Merozoite Surface Protein 2.
Understanding Human-Derived Antibodies Generated by Polymorphic Malaria Vaccine Against Merozoite Surface Protein 2.
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了解多态性疟疾疫苗针对裂殖子表面蛋白产生的人源抗体 2。
DOI：
10.1093/infdis/jiy171
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Angrisano F
中科院分区：
文献类型：
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作者：
Angrisano F
仍然需要一种有效的疟疾疫苗，以加强控制和消除工作。2017年世界卫生组织年度报告强调了这一点，表明在多个领域，最近在减轻疾病负担方面取得的进展正在停滞和逆转。在研制有效的抗疟疾疫苗过程中，一个持续存在的挑战是，主要候选疫苗bbb的遗传多态性和随后的抗原多样性率异常。人类疟疾免疫的关键靶抗原和主要疫苗候选抗原（如AMA1、MSP1）已经进化出显著的多态性，以逃避免疫。这给疟疾疫苗的开发带来了持续的挑战，因为它对逻辑设计的实验室衍生疫苗的实际有效性有重大影响。高免疫原性蛋白结构域的抗原多态性已发展成为寄生虫的重要免疫逃避机制。对假定的血液期疫苗进行的几项试验已经证明了菌株特异性效力的证据，这最终有助于确定疫苗是否有效[4-6]。自然获得的疟疾免疫通常发展缓慢，需要长期反复接触疟疾；这种缓慢的获取部分归因于需要开发足够广泛的针对不同菌株的抗体库[7,8]。目前克服抗原多样性和疫苗逃逸的疫苗策略包括结合多个等位基因，开发具有修饰序列的抗原以增强有效的免疫原性，或靶向保守或多样性较少的区域和表位[3]。关于自然获得或疫苗诱导的人类免疫应答对候选疫苗的特异性和交叉反应性的知识仍然有限。支持交叉反应反应发展的条件和方法可能通过抗原多样性限制免疫逃逸，这在很大程度上是未知的。在这一期的《感染性疾病杂志》上，Feng， Boyle等人利用表征良好的merozoite表面蛋白MSP2作为模型，更好地了解疫苗产生的人源性抗体与自然获得性反应的特异性和功能，确定MSP2联合疫苗是否成功产生针对多种恶性疟原虫菌株的功能性抗体，并评价疫苗诱导抗体的整体特异性。使用
There is a continuing need for an effective malaria vaccine to enhance control and elimination efforts. This has been highlighted in the 2017 World Health Organization annual report, indicating that in multiple areas recent advances in reducing disease burden are stalling and reversing [1]. One continuing challenge in the development of effective antimalarial vaccine is the phenomenon of exceptional rates of genetic polymorphism and subsequent antigenic diversity in leading vaccine candidates [2]. Key target antigens of human immunity to malaria and leading vaccine candidate antigens (eg, AMA1, MSP1), have evolved significant polymorphisms in order to evade immunity. This has presented a persistent challenge in malaria vaccine development as it significantly impacts on how practically efficacious a logically designed, laboratory-derived vaccine is [3]. Antigenic polymorphisms in protein domains of high immunogenicity have evolved to be a crucial immune evasion mechanism of the parasite. Several trials of putative blood-stage vaccines have demonstrated evidence of strain-specific efficacy, which ultimately contributes towards rendering a vaccine effective or ineffective [4–6]. Naturally acquired immunity to malaria is typically slow to develop and requires repeated exposure to malaria over time; this slow acquisition is attributed, in part, to the requirement for the development of a sufficiently broad repertoire of antibodies against diverse strains [7, 8]. Current vaccine strategies to overcome antigenic diversity and vaccine escape include the incorporation of multiple alleles, developing antigens with modified sequences to enhance effective immunogenicity, or targeting conserved or less-diverse regions and epitopes [3]. Knowledge regarding the specificity and cross-reactivity of naturally acquired or vaccine-induced human immune responses to vaccine candidates is still limited. The conditions and approaches that favor the development of cross-reactive responses that may limit immune escape through antigenic diversity are largely unknown.In this issue of the Journal of Infectious Disease, Feng, Boyle et al use the well-characterized merozoite surface protein, MSP2, as a model to better understand the specificity and function of human-derived antibodies generated by vaccines compared with naturally acquired responses, determine whether an MSP2 combination vaccine successfully generated functional antibodies to multiple Plasmodium falciparum strains, and evaluate the overall specificity of vaccine-induced antibodies. Using