Instituto René Rachou/FIOCRUZ Minas, Belo Horizonte, Minas Gerais, Brazil.
Center for Global Health and Infectious Diseases Research, Department of Global Health, College of Public Health, University of South Florida, Tampa, Florida, United States of America.
PLoS Negl Trop Dis. 2022 Aug 3;16(8):e0010305. doi: 10.1371/journal.pntd.0010305. eCollection 2022 Aug.
The simultaneous infection of Plasmodium falciparum and Epstein-Barr virus (EBV) could promote the development of the aggressive endemic Burkitt's Lymphoma (eBL) in children living in P. falciparum holoendemic areas. While it is well-established that eBL is not related to other human malaria parasites, the impact of EBV infection on the generation of human malaria immunity remains largely unexplored. Considering that this highly prevalent herpesvirus establishes a lifelong persistent infection on B-cells with possible influence on malaria immunity, we hypothesized that EBV co-infection could have impact on the naturally acquired antibody responses to P. vivax, the most widespread human malaria parasite.
METHODOLOGY/PRINCIPAL FINDINGS: The study design involved three cross-sectional surveys at six-month intervals (baseline, 6 and 12 months) among long-term P. vivax exposed individuals living in the Amazon rainforest. The approach focused on a group of malaria-exposed individuals whose EBV-DNA (amplification of balf-5 gene) was persistently detected in the peripheral blood (PersVDNA, n = 27), and an age-matched malaria-exposed group whose EBV-DNA could never be detected during the follow-up (NegVDNA, n = 29). During the follow-up period, the serological detection of EBV antibodies to lytic/ latent viral antigens showed that IgG antibodies to viral capsid antigen (VCA-p18) were significantly different between groups (PersVDNA > NegVDNA). A panel of blood-stage P. vivax antigens covering a wide range of immunogenicity confirmed that in general PersVDNA group showed low levels of antibodies as compared with NegVDNA. Interestingly, more significant differences were observed to a novel DBPII immunogen, named DEKnull-2, which has been associated with long-term neutralizing antibody response. Differences between groups were less pronounced with blood-stage antigens (such as MSP1-19) whose levels can fluctuate according to malaria transmission.
CONCLUSIONS/SIGNIFICANCE: In a proof-of-concept study we provide evidence that a persistent detection of EBV-DNA in peripheral blood of adults in a P. vivax semi-immune population may impact the long-term immune response to major malaria vaccine candidates.
疟原虫和 Epstein-Barr 病毒（EBV）的同时感染可能会促进在疟原虫全疫区生活的儿童中侵袭性地方性伯基特淋巴瘤（eBL）的发展。虽然已经证实 eBL与其他人类疟原虫无关，但 EBV 感染对人类疟疾免疫产生的影响在很大程度上仍未得到探索。考虑到这种高度流行的疱疹病毒在 B 细胞上建立了终生持续感染，并可能对疟疾免疫产生影响，我们假设 EBV 合并感染可能对最广泛的人类疟原虫寄生虫——间日疟原虫的自然获得性抗体反应产生影响。
方法/主要发现：本研究设计包括在亚马逊雨林中对长期间日疟原虫暴露的个体进行的三次横断面调查（基线、6 个月和 12 个月），每六个月进行一次。该方法主要针对一组 EBV-DNA（balf-5 基因扩增）在周围血液中持续检测到的疟原虫暴露个体（PersVDNA，n=27）和一组年龄匹配的 EBV-DNA 在随访期间从未检测到的疟原虫暴露个体（NegVDNA，n=29）。在随访期间，对 EBV 抗体裂解/潜伏病毒抗原的血清学检测显示，病毒衣壳抗原（VCA-p18）的 IgG 抗体在两组之间存在显著差异（PersVDNA > NegVDNA）。一组涵盖广泛免疫原性的血期疟原虫抗原证实，一般来说，与 NegVDNA 相比，PersVDNA 组的抗体水平较低。有趣的是，与一种新型 DBPII 免疫原 DEKnull-2 观察到更显著的差异，该免疫原与长期中和抗体反应有关。与血期抗原（如 MSP1-19）相比，两组之间的差异不太明显，血期抗原的水平可能根据疟疾传播而波动。
在一项概念验证研究中，我们提供了证据，证明在间日疟原虫半免疫人群中，外周血中 EBV-DNA 的持续检测可能会影响对主要疟疾候选疫苗的长期免疫反应。
