Cutts Julia C, Powell Rosanna, Agius Paul A, Beeson James G, Simpson Julie A, Fowkes Freya J I
BMC Med. 2014 Sep 9;12:150. doi: 10.1186/s12916-014-0150-1.
Identifying Plasmodium vivax antigen-specific antibodies associated with P. vivax infection and protective immunity is key to the development of serosurveillance tools and vaccines for malaria. Antibody targets of P. vivax can be identified by seroepidemiological studies of individuals living in P. vivax-endemic areas, and is an important strategy given the limited ability to culture P. vivax in vitro. There have been numerous studies investigating the association between P. vivax antibody responses and P. vivax infection, but there has been no standardization of results to enable comparisons across populations.
We performed a systematic review with meta-analysis of population-based, cross-sectional, case-control, and cohort studies of individuals living in P. vivax-endemic areas. We searched 6 databases and identified 18 studies that met predefined inclusion and quality criteria, and examined the association between antibody responses to P. vivax antigens and P. vivax malaria.
The majority of studies were published in South America (all from Brazil) and the rest from geographically diverse areas in the Asia-Pacific region. Considerable heterogeneity in estimates was observed, but IgG responses to PvCSP, PvMSP-119, PvMSP-9RIRII, and PvAMA1 were associated with increased odds of P. vivax infection in geographically diverse populations. Potential sources of heterogeneity included study design, different transmission intensities and transmigrant populations. Protective associations were observed for antibodies to PvMSP-119, PvMSP-1NT, PvMSP-3α and PvMSP-9NT antigens, but only in single geographical locations.
This systematic review revealed several antigen-specific antibodies that were associated with active infection and protective immunity, which may be useful biomarkers. However, more studies are needed on additional antigens, particularly cohort studies to increase the body of evidence for protective immunity. More studies representing diverse geographical regions encompassing varying P. vivax endemicities are needed to validate the generalizability of the findings and to provide a solid evidence base for the use of P. vivax antigens in vaccines and serosurveillance tools.
鉴定与间日疟原虫感染及保护性免疫相关的间日疟原虫抗原特异性抗体，是开发疟疾血清学监测工具和疫苗的关键。可通过对生活在间日疟原虫流行地区的个体进行血清流行病学研究来确定间日疟原虫的抗体靶点，鉴于间日疟原虫体外培养能力有限，这是一项重要策略。已有众多研究调查间日疟原虫抗体反应与间日疟原虫感染之间的关联，但结果尚无标准化，无法在不同人群间进行比较。
我们对生活在间日疟原虫流行地区的个体进行了基于人群的横断面、病例对照和队列研究的系统评价及荟萃分析。我们检索了6个数据库，确定了18项符合预定义纳入标准和质量标准的研究，并检验了对间日疟原虫抗原的抗体反应与间日疟原虫疟疾之间的关联。
大多数研究发表于南美洲（均来自巴西），其余来自亚太地区不同地理区域。观察到估计值存在相当大的异质性，但在不同地理区域的人群中，对间日疟原虫环子孢子蛋白（PvCSP）、间日疟原虫裂殖子表面蛋白1 19 kDa片段（PvMSP-119）、间日疟原虫裂殖子表面蛋白9富含精氨酸/异亮氨酸重复区域（PvMSP-9RIRII）和间日疟原虫顶膜抗原1（PvAMA1）的IgG反应与间日疟原虫感染几率增加相关。异质性的潜在来源包括研究设计、不同的传播强度和移民人群。观察到对PvMSP-119、间日疟原虫裂殖子表面蛋白1 N端（PvMSP-1NT）、间日疟原虫裂殖子表面蛋白3α（PvMSP-3α）和间日疟原虫裂殖子表面蛋白9 N端（PvMSP-9NT）抗原的抗体具有保护关联，但仅在单一地理位置观察到。
本系统评价揭示了几种与活动性感染和保护性免疫相关的抗原特异性抗体，它们可能是有用的生物标志物。然而，需要对更多抗原进行研究，尤其是队列研究，以增加保护性免疫的证据。需要更多代表不同地理区域、涵盖不同间日疟原虫流行程度的研究，以验证研究结果的普遍性，并为在疫苗和血清学监测工具中使用间日疟原虫抗原提供坚实的证据基础。
