Kirby Institute for Infection and Immunity, UNSW Australia, Sydney, NSW, 2052, Australia.
Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH, USA.
Malar J. 2019 Jan 22;18(1):19. doi: 10.1186/s12936-019-2657-6.
Studies of the association between the level of anti-malarial antibody and protection from malaria infection can yield conflicting results if they fail to take into account differences in the malaria transmission rate. This can occur because high malaria exposure may drive high antibody responses, leading to an apparent positive association between immune response and infection rate. The neonatal period provides a unique window to study the protective effects of antibodies, because waning maternally-derived antibodies lead to different levels of protection with time.
This study uses data from two well-defined infant cohorts in Western Kenya with different burdens of malaria transmission. Survival models were used to assess how the magnitude of maternally derived malaria-specific IgG antibody (to 24 malaria antigens measured using Luminex beads) affected the time-to-first Plasmodium falciparum infection (detected by PCR). In addition, mathematical models were used to assess how the frequency of malaria infection varied between the cohorts with different exposure levels.
Despite differences in underlying malaria incidence in the two regions, there was no difference in time-to-first malaria infection between the cohorts. However, there was a significant period of protection observed in children with high initial MSP1 (42 kDa fragment)-specific antibody levels, but this protection was not observed in children with low antibody levels. Children from the high transmission cohort had both longer initial periods of protection from malaria (attributable to higher initial antibody levels), but more rapid time-to-first-infection once malaria specific maternal antibodies declined below protective levels (attributable to higher exposure rates).
This study demonstrates the complex interaction between passive (maternally-derived) immunity and the degree of malaria exposure in infants. Children from regions of high malaria transmission had higher levels of maternally-derived antibodies in early life, which led to a significant protection for several months. However, once this immunity waned, the underlying higher frequency of infection was revealed. A better understanding of the interaction between malaria exposure, immunity, and transmission risk will assist in identifying protective immune responses in P. falciparum infection.
如果未能考虑疟疾传播率的差异，研究抗疟抗体水平与疟疾感染保护之间的关联可能会得出相互矛盾的结果。这可能是因为高疟疾暴露可能会导致高抗体反应，从而导致免疫反应与感染率之间出现明显的正相关。新生儿期为研究抗体的保护作用提供了一个独特的窗口，因为母体衍生抗体的衰减会随着时间的推移导致不同程度的保护。
本研究利用来自肯尼亚西部两个具有不同疟疾传播负担的婴儿队列的数据。生存模型用于评估母体来源的疟疾特异性 IgG 抗体（使用 Luminex 珠检测 24 种疟疾抗原）的大小如何影响首次感染恶性疟原虫的时间（通过 PCR 检测）。此外，数学模型用于评估具有不同暴露水平的队列之间疟疾感染频率的变化。
尽管两个地区的基础疟疾发病率存在差异，但两个队列之间的首次疟疾感染时间没有差异。然而，在初始 MSP1（42 kDa 片段）特异性抗体水平较高的儿童中观察到了显著的保护期，但在抗体水平较低的儿童中未观察到这种保护。来自高传播率队列的儿童都有更长的初始疟疾保护期（归因于更高的初始抗体水平），但一旦疟疾特异性母体抗体下降到保护水平以下，首次感染的时间就会更快（归因于更高的暴露率）。
本研究表明，被动（母体衍生）免疫与婴儿疟疾暴露程度之间存在复杂的相互作用。来自疟疾传播率高的地区的儿童在生命早期具有更高水平的母体衍生抗体，这导致了几个月的显著保护。然而，一旦这种免疫力减弱，潜在的更高感染频率就会显现出来。更好地了解疟疾暴露、免疫和传播风险之间的相互作用将有助于确定恶性疟原虫感染的保护性免疫反应。
